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Prenatal stress and postnatal development of neonatal rats - Sex-dependent effects on emotional behavior and learning ability of neonatal rats

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Abstract

Maternal sound stress (800 Hz; 77 dB, every other minute for 15 min/day, from day 10 to 18 of gestation), combined with forced swimming stress (15 min/day), was found to cause potentiation of sound-induced loss of locomotor activity, referred to as emotional behavior, of male offspring, but not that of female offspring, at 4 weeks of age. Maternal stress also caused an increase in the total number of errors by male, but not female offspring in the water-maze test at 6 weeks of age. These effects of stress on emotional behavior and learning behavior were abolished when dams were pretreated with buspirone (30 min before the stress, from day 8 to 18 of gestation). Thus, prenatal stress might have sex-dependent effects on emotional behavior and learning ability of neonatal rats.

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... Cumulatively, studies indicate that PNS alone or in combination with other stresses is linked to higher levels of corticosterone at rest (Jafari et al., 2017d(Jafari et al., , 2019aWeinstock et al., 1998Weinstock et al., , 1992 and increased vulnerability and decreased habituation to novel environments or stressful stimuli (Fride et al., 1986a(Fride et al., , 1985Jafari et al., 2017Jafari et al., , 2019aWeinstock et al., 1992) and in response to an acute stress (Soares-Cunha et al., 2018;Weinstock et al., 1998), as well as enhanced activation of the sympathetic nervous system (Weinstock et al., 1998). PNS also has been shown to be associated with anxious-and/or depressive-like behaviours (Fride and Weinstock, 1989;Jafari et al., 2017dJafari et al., , 2018bMeek et al., 2000;Soares-Cunha et al., 2018;Wakshlak and Weinstock, 1990), impaired spatial learning and memory (Guan et al., 2016;Jafari et al., 2019a;Jafari et al., 2017d;Jafari et al., 2019b;Kim et al., 2013;Nishio et al., 2001), reduced hippocampal synaptic activity (lower level of LTP) (Barzegar et al., 2015) and neurogenesis in dentate gyrus (Kim et al., 2013), decreased hippocampal BDNF (Guan et al., 2016), increased DA turnover (Fride and Weinstock, 1987), delay in sensory and motor development (Fride et al., 1986b;Fride and Weinstock, 1984;Meek et al., 2000;Nishio et al., 2001), and higher incidence of stress-related defecation (Wakshlak and Weinstock, 1990;Weinstock et al., 1992). A PNS study also demonstrated stronger negative alterations of locomotion, exploration, and reactivity of the HPAaxis (high plasma concentration of ACTH and adrenal hypertrophy) than restraint stress or to the combination of both stressors (Badache et al., 2017). ...
... Cumulatively, studies indicate that PNS alone or in combination with other stresses is linked to higher levels of corticosterone at rest (Jafari et al., 2017d(Jafari et al., , 2019aWeinstock et al., 1998Weinstock et al., , 1992 and increased vulnerability and decreased habituation to novel environments or stressful stimuli (Fride et al., 1986a(Fride et al., , 1985Jafari et al., 2017Jafari et al., , 2019aWeinstock et al., 1992) and in response to an acute stress (Soares-Cunha et al., 2018;Weinstock et al., 1998), as well as enhanced activation of the sympathetic nervous system (Weinstock et al., 1998). PNS also has been shown to be associated with anxious-and/or depressive-like behaviours (Fride and Weinstock, 1989;Jafari et al., 2017dJafari et al., , 2018bMeek et al., 2000;Soares-Cunha et al., 2018;Wakshlak and Weinstock, 1990), impaired spatial learning and memory (Guan et al., 2016;Jafari et al., 2019a;Jafari et al., 2017d;Jafari et al., 2019b;Kim et al., 2013;Nishio et al., 2001), reduced hippocampal synaptic activity (lower level of LTP) (Barzegar et al., 2015) and neurogenesis in dentate gyrus (Kim et al., 2013), decreased hippocampal BDNF (Guan et al., 2016), increased DA turnover (Fride and Weinstock, 1987), delay in sensory and motor development (Fride et al., 1986b;Fride and Weinstock, 1984;Meek et al., 2000;Nishio et al., 2001), and higher incidence of stress-related defecation (Wakshlak and Weinstock, 1990;Weinstock et al., 1992). A PNS study also demonstrated stronger negative alterations of locomotion, exploration, and reactivity of the HPAaxis (high plasma concentration of ACTH and adrenal hypertrophy) than restraint stress or to the combination of both stressors (Badache et al., 2017). ...
... Although the limbic system is rich in glucocorticoid receptors, these receptors also are found in most parts of the motor system including motor cortex, cerebellum, basal ganglia (Ahima and Harlan, 1990;Harle et al., 2017), and white matter of the spinal cord (Marlier et al., 1995). Evidence commonly suggests that hyperactivity of the HPA-axis due to PNS can modulate temporal and spatial aspects of motor performance in skilled movements and balance coordination (Fride et al., 1986b;Jafari et al., 2017dJafari et al., ,a, 2019bNishio et al., 2001). Longitudinal human studies also affirm that prenatal stress or anxiety during pregnancy negatively modulates infant neuromotor development (Grace et al., 2016;van Batenburg-Eddes et al., 2009). ...
Article
This review examines the adverse impacts of different noise exposure paradigms on the neuroendocrine system, hippocampal and neocortical structures, cognitive performances, and the development of Alzheimer's disease (AD)-like neuropathological changes in the brain of laboratory animals. Studies were reviewed in three periods during the lifespan including: adult animals exposed to noise, female rodents exposed to noise during gestation, and offspring exposed to noise during the prenatal period. Findings imply that chronic noise exposure dysregulates the neuroendocrine system leading to hyperactivation of the sympathetic divisions of the autonomic nervous system (i.e., the hypothalamic-pituitary-adrenal (HPA)-axis), and increases stress hormones that affect brain and behaviour. Enduring dysregulation of the HPA-axis was the most discussed mechanism for the harmful effect of noise during the lifespan. Studies also suggest a causative association of noise with diverse indicators of the AD-like neuropathology in rodents and a hypersusceptibility in females. The results indicate the importance of future neuroimaging studies to quantify the potential contribution of noise in predisposing cognitive decline and preclinical signs of dementia in humans.
... Yet, due to the lack of studies coupled with the lack of regulations on space requirements for goats in many countries in Europe [30], goats are often kept in densities higher than 1.0 m 2 . Furthermore, studies of prenatal stress most commonly use non-social stressors such as restraint [6,15,[31][32][33][34][35][36], exposure to bright lights [16,32,37,38] or loud noises [12,39] or injections of various substances [4,[39][40][41][42][43], among others. As Kaiser and Sachser [7] point out, however, the manner in which most stressors are applied in the experimental setting do not exist in the animal's natural habitat. ...
... Yet, due to the lack of studies coupled with the lack of regulations on space requirements for goats in many countries in Europe [30], goats are often kept in densities higher than 1.0 m 2 . Furthermore, studies of prenatal stress most commonly use non-social stressors such as restraint [6,15,[31][32][33][34][35][36], exposure to bright lights [16,32,37,38] or loud noises [12,39] or injections of various substances [4,[39][40][41][42][43], among others. As Kaiser and Sachser [7] point out, however, the manner in which most stressors are applied in the experimental setting do not exist in the animal's natural habitat. ...
... A large amount of data indicates that prenatal stress manifests itself in males and females differently. Females generally appear to display a larger increase in anxiety-like behaviors than males [2,3,9,42,56] while males show increased learning deficits [3,9,32,39]. In accordance to these studies, males tended to be less social during the social test. ...
Article
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Prenatal stress (stress experienced by a pregnant mother) and its effects on offspring have been comprehensively studied but relatively little research has been done on how prenatal social stress affects farm animals such as goats. Here, we use the operational description of 'stress' as "physical or perceived threats to homeostasis." The aim of this study was to investigate the prenatal effects of different herd densities on the fear responses and sociality of goat kids. Pregnant Norwegian dairy goats were exposed to high, medium or low prenatal animal density treatments throughout gestation (1.0, 2.0 or 3.0 m2 per animal, respectively). One kid per litter was subjected to two behavioral tests at 5 weeks of age. The 'social test' was applied to assess the fear responses, sociality and social recognition skills when presented with a familiar and unfamiliar kid and the 'separation test' assessed the behavioral coping skills when isolated. The results indicate goat kids from the highest prenatal density of 1.0 m2 were more fearful than the kids from the lower prenatal densities (i.e. made more escape attempts (separation test: P < 0.001) and vocalizations (social test: P < 0.001; separation test: P < 0.001). This effect was more pronounced in females than males in the high density (vocalizations; social test: P < 0.001; separation test: P = 0.001) and females were generally more social than males. However, goat kids did not differentiate between a familiar and an unfamiliar kid at 5 weeks of age and sociality was not affected by the prenatal density treatment. We conclude that high animal densities during pregnancy in goats produce offspring that have a higher level of fear, particularly in females. Behavioral changes in offspring that occur as an effect of prenatal stress are of high importance as many of the females are recruited to the breeding stock of dairy goats.
... Behavioral effects of developmental (perinatal) exposure to Al have been examined to some extent using laboratory rodents (Colomina et al., 1999;Gonda and Lehotzky, 1996;Gonda et al., 1997;Santucci et al., 1994;Abu-Taweel et al., 2012). Maternal stress during pregnancy can have serious negative effects on the learning abilities of the offspring (Nishio et al., 2001;Sternberg and Ridgway, 2003). Exposure to Al during pregnancy along with maternal stress can further have serious interactions and result into learning defects in the offspring (Colomina et al., 2005;Roig et al., 2006). ...
... Gestational and lactational exposure to Al doses can result in persistent neurobehavioural deficits in the offspring of some mammals (Roig et al., 2006). Studies in rodents have also demostrated that during pregnancy, exposure to Al causes long-lasting effects on emotionality and learning capabilities (Nishio et al., 2001;Sternberg and Ridgway, 2003;Shaw and Petrik, 2009;Kumar et al., 2009). Al exposure in animals and humans results in behavioral changes and intellectual impairment and it is possible that the behavioral changes could be the result of subtle changes in the serotonin level of the brain regions following Al exposure (Kumar, 2002). ...
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Aluminium (Al) is a well-known neurotoxicant in adults as well as in developing stages of animals and humans. Al is reported in the etiology of several neurodegenerative disorders like Parkinson’s disease, dementia, and Alzheimer’s disease. Besides multiple exposure opportunities for early exposure of the fetus to Al, the route or mode of exposure is also critical for the developing offspring. Al-induced behavioral alterations as well as cognitive deficits and rodent brain neurotransmitters level, have been widely reported in literature but exact mechanism in the offspring of perinatally Al exposed dams is not yet understood properly and needs more attention. In the present study, the perinatal oral exposure of the dams to 300 and 600 mg/kg Al (aluminium chloride) resulted in a significant and dose-dependent reduction in postnatal body weight gain, delays in opening of the eyes and appearance in the body hair fuzz, and deficits in the sensory motor reflexes of the mice pups during weaning period (from the day of birth to postnatal day 21). At adolescent and adult ages of the male offspring, a significant and dose-dependent deficit was also observed in their learning capability (at postnatal day-PD25), and cognitive behavior (at PD30-36). Furthermore, a significant and dosedependent disturbance in the levels of neurotransmitters like dopamine (DA) and serotonin (5-HT); non enzymatic oxidative stress (OS) indices like thiobarbituric acidractive substances (TBARS) and total reduced glutathione (GSH); and enzymatic OS indices like glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were observed in the forebrain region of the offspring at post-natal day (PD)7, PD14, PD21, PD30, and PD36. Thus, perinatal Al exposure can affect the in utero developing fetus, raising the concerns that during a critical prenatal and postnatal period of brain development, Al exposure has potential neurotoxic hazards and might modify the properties of the dopaminergic system and inflicts OS that changes the threshold of that system or other related systems resulting into a longer lasting cognitive dysfunction. A reduced use of Al during pregnancy is of crucial importance in preventing Al-induced neurotoxicity in the offspring.
... The effects of PS are also observed in animals with increases in the latency to play (Takahashi et al., 1992), nondirected locomotor behavior (i.e., pacing) (Coe et al., 2003), anxiety (Estanislau and Morato, 2005;Fride and Weinstock, 1988;Vallee et al., 1997), and decreases in learning and memory (Gué et al., 2004;Lemaire et al., 2000;Nishio et al., 2001;Son et al., 2006;Wu et al., 2007;Yang et al., 2006), and focused exploration (Coe et al., 2003). In animals, PS is also associated with greater distractibility and attention deficits (Schneider and Coe, 1993;Schneider et al., 1999) as well as delayed object permanence (Schneider, 1992), an early indicator of cognitive development. ...
... Prenatal stress has been linked to abnormal outcomes in rodents, non-human primates, and humans (Anderson et al., 1985;Barros et al., 2006;Beversdorf et al., 2005;Coe et al., 2002Coe et al., , 2003Crandon, 1979;Estanislau and Morato, 2005;Fleming et al., 1986;Fride and Weinstock, 1988;Fujioka et al., 2006;Grizenko et al., 2008;Gué et al., 2004;Hayashi et al., 1998;Henry et al., 1994;Huttenen and Niskanen, 1978;Jones et al., 1997;Kawamura et al., 2006;Kerchner and Ward, 1992;Kerchner et al., 1995;King and Laplante, 2005;Kinney et al., 1999a,b;Kinney, 2001;Kinney et al., 2008a,b;Kraszpulski et al., 2006;Laplante et al., 2004Laplante et al., , 2008Lemaire et al., 2000Lemaire et al., , 2006Linnet et al., 2003;McIntosh et al., 1995;Michelsen et al., 2007;Murmu et al., 2006;Nishio et al., 2001;O'Connor et al., 2002O'Connor et al., , 2003Poland et al., 1999;Rhees et al., 1999;Rodriguez and Bohlin, 2005;Salm et al., 2004;Schmitz et al., 2002;Schneider, 1992;Schneider and Coe, 1993;Schneider et al., 1999;Son et al., 2006;Szuran et al., 1994Szuran et al., , 2000Talge et al., 2007;Ulupinar and Yucel, 2005;Ulupinar et al., 2006;Uno et al., 1994;Vallee et al., 1997;van Os and Selten, 1998;Watson et al., 1999;Weinstock et al., 1992;Wu et al., 2007;Yang et al., 2006;Zuena et al., 2008). It is clear from animal studies that PS affects the morphology of the offsprings' brains, but the mechanisms that lead to these effects remain poorly understood. ...
Article
Background: Psychosocial stress during pregnancy has been proposed as a major contributor of glucocorticoid-mediated programming of the fetal hypothalamic-pituitary adrenal (HPA) axis, with later adverse health consequences. However, evidence linking maternal stress to maternal cortisol values during pregnancy is inconclusive. A possible explanation for this is that other maternal factors overshadow any potential effects of stress on cortisol levels. We studied a large cohort of pregnant women with extensive data on pregnancy characteristics to determine the respective contributions of biological, environmental and psychosocial stress factors to cortisol levels in pregnancy. Methods: We used data from 3039 women from the Amsterdam Born Children and their Development-study cohort. Serum cortisol was measured in blood, collected at the first prenatal visit, at different gestational ages (median=91days, range=40-256days), and at various time points during the day (median=11:45h, range=08:00-18:30h). We assessed associations between maternal serum cortisol in pregnancy and biological factors, lifestyle factors and stress factors, including depression, anxiety, pregnancy-related anxiety, work stress, parenting stress and fatigue. Results: In multivariable analysis, variables that were associated with higher cortisol levels in pregnancy were lower maternal age [1.5nmol/l, 95%CI (0.6-2.4)], being nulliparous [21.5 nmol/l (15.9-27.1)], lower pre-pregnancy body mass index (BMI) [1.3nmol/l (0.3-2.4)], higher C-reactive protein (CRP) [1.0nmol/l (0.4-1.5)], carrying a female fetus [9.2nmol/l (1.8-16.5)], non-smoking [14.2nmol/l (0.6-27.7)], sufficient sleep [8.5nmol/l (0.9-16.1)], and being unemployed [12.7nmol/l (2.2-23.2)]. None of the psychosocial stressors was significantly associated with serum cortisol levels in pregnancy. A total of 32% of all variance in cortisol was explained by gestational age, maternal age, time of day, parity, pre-pregnancy BMI, CRP, fetal sex, smoking behavior, self-reported sleep sufficiency, and employment. Conclusions: Our data suggest that maternal cortisol during pregnancy is mainly affected by biological and lifestyle factors, but not by psychosocial factors. We suggest that psychosocial stress in pregnancy might program the fetus through other mechanisms than through altering maternal cortisol levels.
... Studies show that maternal stress and maternal exposure to Flx both have long-term effects on the mouse and rat offspring. These maternal experiences alter offspring's learning and memory (stress: [20][21][22][23][24][25]; Flx: [26][27][28]), aggression levels (stress: [29][30][31][32]; Flx: [28,[32][33][34]), circadian behaviours (stress: [35]; Flx: [36]), and depressive-and anxiety-like behaviours (stress: [25,[37][38][39]; Flx: [26][27][28][40][41][42][43]). ...
... Second, male and female animals are differently affected by stress [54][55][56][57] and Flx administration [58][59][60]. And, most importantly, male and female mice show different patterns of behavioural changes following maternal stress [22,23,[61][62][63][64][65] and perinatal Flx administration [43,63,66]. ...
Article
Methods: Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day 7 to E18), or FLX (E15- postnatal day 12), or a combination of stress and FLX or left untreated. At two months of age, the female offspring went through a comprehensive behavioural test battery. Results: Maternal stress led to increased activity and alterations of prepulse inhibition in the adult female offspring. Maternal treatment with Flx had a potentially beneficial effect on spatial memory. The combination of prenatal stress and perinatal Flx exposure did not interact in their effects. These results suggest that gestational Flx exposure may have a limited negative impact on female offspring.
... The sexual dimorphism found in locomotor activity with the OF test (total crossings + rearings) has already been reported in rodents (Wakshlak and Weinstock, 1990; Pallarés et al., 2007;), females being always more active than males in this kind of test. Also, vulnerability to early stress has been seen previously in the OF test (Wigger and Neumann, 1999; Nishio et al., 2001;). According to these authors, the effects of PS are more pronounced in males, these proving to be more emotional during the OF test. ...
... According to these authors, the effects of PS are more pronounced in males, these proving to be more emotional during the OF test. For instance, Nishio et al. (2001) reported a decrease in motor activity in neonate PS males, no effects being observed for PS females. In the OF test, animals face contradictory motivations—the fear of an open enlightened environment, and the motivation to explore it (novelty preference) (Archer, 1973). ...
... The entire litter was measured for body weight (PND 4, 10, 15, 21, 30, 45, 60, 75 and 90) and development of physical landmarks including pinna detachment (PND 1-5), eye opening (PND 13-15) and testis descent (PND [22][23][24][25][26][27][28][29]. ...
... Prenatal restraint stress did not produce any differences in whole litter body weight between prenatal stressed offsprings and their control littermates at PND3 and throughout PND 90. This is in agreement with a recent study, which reported that maternal sound stress combined with forced swimming stress, resulted in no differences in body weight among offsprings (28). Ear and eye opening days were not different among control and stressed offsprings. ...
Article
Prenatal stress greatly influences the ability of an individual to manage stressful events in adult-hood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D 2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA 1 region and core region of nucleus accum-bens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA 1 , medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders.
... Exposure to environmental stress during pregnancy is of great importance because exposures in early developmental stage can affect the maturation of the offspring in pregnant women (23,24). Prenatal stress results in learning, behavioral and emotional changes in later life though the mechanisms underlying such effects are not fully understood (25). ...
... It was demonstrated that a combination of noise stress and forced swimming clearly affected both the emotional behavior and the learning ability of the offspring in a sex-dependent manner (i.e. observed only in male offspring) (23,27). The finding in rodents that prenatal stress can cause deficiencies in some early indices of physical maturation and also that these deficiencies can be continued into adulthood are consistent with those in humans. ...
Article
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Objectives: There is much evidence indicating that depression is influenced by the levels of neurotransmitters such as dopamine, GABA and adrenaline. The current study we designed to investigate the effect of exposure of pregnant rats to different colors on neurotransmitters level, as indicators of mood disorders in off springs. Materials and methods: Five groups of pregnant female Wistar rats (eight rats in each group) were enrolled in this study. Dopamine, adrenaline and GABA concentration in sera of rats were measured using ELISA. Results: The colors black and red elevated the GABA levels in serum and CSF while the colors green and blue decreased the GABA levels. The colors black and red also decreased the sera and CSF levels of dopamine compared to the control group. The concentration of adrenaline was increased following exposure to the colors black, red and blue but decreased only following color green exposure. These results showed serious changes in neurotransmitter levels due to exposure to different colors which can be translated as mood and behavior changes. Conclusion: It can be concluded that exposure during pregnancy can lead to postpartum behavioral changes even at adulthood and such changes can be made by colors.
... The effects of PS are also observed in animals with increases in the latency to play (Takahashi et al., 1992), nondirected locomotor behavior (i.e., pacing) (Coe et al., 2003), anxiety (Estanislau and Morato, 2005;Fride and Weinstock, 1988;Vallee et al., 1997), and decreases in learning and memory (Gué et al., 2004;Lemaire et al., 2000;Nishio et al., 2001;Son et al., 2006;Wu et al., 2007;Yang et al., 2006), and focused exploration (Coe et al., 2003). In animals, PS is also associated with greater distractibility and attention deficits (Schneider and Coe, 1993;Schneider et al., 1999) as well as delayed object permanence (Schneider, 1992), an early indicator of cognitive development. ...
... Prenatal stress has been linked to abnormal outcomes in rodents, non-human primates, and humans (Anderson et al., 1985;Barros et al., 2006;Beversdorf et al., 2005;Coe et al., 2002Coe et al., , 2003Crandon, 1979;Estanislau and Morato, 2005;Fleming et al., 1986;Fride and Weinstock, 1988;Fujioka et al., 2006;Grizenko et al., 2008;Gué et al., 2004;Hayashi et al., 1998;Henry et al., 1994;Huttenen and Niskanen, 1978;Jones et al., 1997;Kawamura et al., 2006;Kerchner and Ward, 1992;Kerchner et al., 1995;King and Laplante, 2005;Kinney et al., 1999a,b;Kinney, 2001;Kinney et al., 2008a,b;Kraszpulski et al., 2006;Laplante et al., 2004Laplante et al., , 2008Lemaire et al., 2000Lemaire et al., , 2006Linnet et al., 2003;McIntosh et al., 1995;Michelsen et al., 2007;Murmu et al., 2006;Nishio et al., 2001;O'Connor et al., 2002O'Connor et al., , 2003Poland et al., 1999;Rhees et al., 1999;Rodriguez and Bohlin, 2005;Salm et al., 2004;Schmitz et al., 2002;Schneider, 1992;Schneider and Coe, 1993;Schneider et al., 1999;Son et al., 2006;Szuran et al., 1994Szuran et al., , 2000Talge et al., 2007;Ulupinar and Yucel, 2005;Ulupinar et al., 2006;Uno et al., 1994;Vallee et al., 1997;van Os and Selten, 1998;Watson et al., 1999;Weinstock et al., 1992;Wu et al., 2007;Yang et al., 2006;Zuena et al., 2008). It is clear from animal studies that PS affects the morphology of the offsprings' brains, but the mechanisms that lead to these effects remain poorly understood. ...
... This discrepancy may be due, in part, to differences in maze sizetheirs was significantly smaller than ours. Gestational stress has induced deficits in other tests of spatial learning and memory in both young (Y-maze ; water maze (Nishio et al., 2001;Lemaire et al., 2000)), and mature (water maze (Zargon et al., 2006;Lemaire et al., 2000)) male offspring. However, others have reported no such impairments (Szuran et al., 2000). ...
... In general, animal research has had a relatively narrow experimental focus with the emphasis on birth parameters such as sex ratio, litter size, weight, and the physiological, endocrine, and behavioural profile of adult, male progeny. Only a small number of reports have examined the responses of females (for example, see Burton, Lovic, & Fleming, 2006;Nishio et al. 2001;Szuran et al. 2000). The lack of inclusion of female responses is not representative of clinical findings: in humans, stress-related psychopathology such as anxiety and depression is more commonly experienced by women than men (Eaton et al., 2008;Kendler et al., 2000;Bebbington et al., 1998;Sprock, & Yoder, 1997 There is evidence to suggest that the feto-placental unit may be altered during gestational stress, likely by elevated levels of glucocorticoids (Emack et al., 2008;Mairesse et al., 2007;Hougaard et al., 2005); however, the role of postnatal environmental factors, namely maternal care, cannot be ignored. ...
... The sexual dimorphism found in locomotor activity with the OF test (total crossings + rearings) has already been reported in rodents (Wakshlak and Weinstock, 1990;Pallarés et al., 2007;Duchesne et al., 2009), females being always more active than males in this kind of test. Also, vulnerability to early stress has been seen previously in the OF test (Wigger and Neumann, 1999;Nishio et al., 2001;Zueña et al., 2008). According to these authors, the effects of PS are more pronounced in males, these proving to be more emotional during the OF test. ...
... According to these authors, the effects of PS are more pronounced in males, these proving to be more emotional during the OF test. For instance, Nishio et al. (2001) reported a decrease in motor activity in neonate PS males, no effects being observed for PS females. ...
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Sertraline is a clinically effective Selective Serotonin Reuptake Inhibitor known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behaviour and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to sertraline throughout adolescence on behavioural and physiological developmental parameters in prenatally stressed Wistar rats. Sertraline was administered (5mg/kg/day p.o.) from the age of 1-3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term sertraline treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed ‘catch-up’ growth found in PS females. Neither prenatal stress nor Sertraline treatment induced remarkable alterations in behaviour and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behaviour in the open field, while in females, it impaired startle habituation. In both cases, sertraline treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by sertraline. The present findings are evidence that continuous sertraline administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.
... Studies on diverse organisms have shown that maternal stress can have long-lasting effects on offspring traits including survival [3][4]8,11], growth [4,[12][13][14][15], morphology [4,[14][15][16], and behavior [8,[17][18][19][20]. While stress-induced maternal effects can be mediated by differential provisioning of resources by mothers [2,6], stress-induced maternal effects are often mediated by prenatal exposure to maternally-derived stress hormones. ...
... Further, embryos of predator-exposed mothers were larger, either because they began with more resources (as suggested by [33]) or grew more quickly during early development. Many of the physiological systems involved in the embryonic response to maternal exposure to predation risk are evolutionarily conserved between sticklebacks and mammals [17][18], amphibians [3,23], reptiles [19] and birds [7,60]. Therefore our results identify molecular mechanisms in offspring that might be altered by maternal experience in other organisms. ...
Article
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There is growing evidence for nongenetic effects of maternal experience on offspring. For example, previous studies have shown that female threespined stickleback fish (Gasterosteus aculeatus) exposed to predation risk produce offspring with altered behavior, metabolism and stress physiology. Here, we investigate the effect of maternal exposure to predation risk on the embryonic transcriptome in sticklebacks. Using RNA-sequencing we compared genome-wide transcription in three day post-fertilization embryos of predator-exposed and control mothers. There were hundreds of differentially expressed transcripts between embryos of predator-exposed mothers and embryos of control mothers including several non-coding RNAs. Gene Ontology analysis revealed biological pathways involved in metabolism, epigenetic inheritance, and neural proliferation and differentiation that differed between treatments. Interestingly, predation risk is associated with an accelerated life history in many vertebrates, and several of the genes and biological pathways that were identified in this study suggest that maternal exposure to predation risk accelerates the timing of embryonic development. Consistent with this hypothesis, embryos of predator-exposed mothers were larger than embryos of control mothers. These findings point to some of the molecular mechanisms that might underlie maternal effects.
... In recent years , several studies have investigated the effects of neonatal stress on behavior and stress resistance in animal and human models, and have found that prenatal stress can affect the emotional and cognitive ability of rat pups (Cabrera et al., 1999;Nishio et al., 2001), in addition Furthermore, rhesus monkeys raised in an enriched neonatal environment, have superior performance in orientation and motor activity, with fewer temperamental responses (such as fear) compared to rhesus raised in a less rich environment (Schneider et al., 1991;Bard et al., 2001). Tremblay (2002) suggested that some types of maternal care improve spatial learning and memory of the offspring by increasing hippocampal development. ...
... While this finding may be related to the sex difference observed in uptake of CBD into the fetal brain, it is also possible that this finding reflects an overall sex difference in the sensitivity of the developing brain to perturbations in neurocircuitry underlying spatial memory. For example, maternal exposure to sound stress and forced swimming has been found to cause spatial memory deficits in male offspring, with no effect seen in female offspring, an effect at least partly mediated by a serotonergic mechanism involving 5HT1A receptors [65]. ...
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Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.
... But, in prenatal stress experiments, the vulnerability outcome between sexes seems to also depend largely on the stressor that the dams have been exposed to. For instance, when dams were exposed to sound stress and forced swimming sessions, only the male offspring showed increased emotional reactivity to sound stress and cognitive deficits in the Morris water maze laterthese effects seemed to involve the serotonin 5-HT 1A receptors and were abolished if dams were given an anxiolytic before the stress sessions (Nishio et al., 2001). Mild maternal restraint stress during gestation also resulted in impaired spatial learning in the male offspring only but females, on the other hand, showed more anxiety and depressive-like behaviors, and both the anxiogenic behavior in females and the learning impairment in males were abolished if the dams were previously adrenalectomised (Zagron and Weinstock, 2006). ...
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Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer’s disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson’s, autism spectrum conditions, attention-deficit hyperactivity disorders, Tourette’s syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment.
... 6 Loss of locomotor activity was observed in 4-week-old male offspring, as a result of sound stress combined with forced swim stress their mothers went through, during their late gestation period. 25 Recurrent mental stress in squirrel monkeys throughout gestation, led to diminished motor skills, reduced balance responses, and decreased post-rotary nystagmus in their infants. 26 Relatively, the larger number of studies have suggested that the late gestational period is more sensitive to emotional stressinduced effects on the offspring. ...
... Several factors such as stress (Nishio et al., 2001;Shors, 2004), aging (De Bartolo et al., 2010;Weiler et al., 2008), repetition (Toppino and Bloom, 2002) and reward value (Adcock et al., 2006;Kruidhof et al., 2012;Hoedjes et al., 2011) may affect the learning ability and memory retention of animals. Reward value can affect different behaviors such as flower odor preference in honeybees (Russell et al., 2016), win-shift tendency in birds (shift away from/ avoid locations that have recently yielded food) (Sulikowski and Burke, 2007), as well as changes in the duration of memory, e.g. for odors in fruit flies (Burke and Waddell, 2011). ...
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Upon encountering a host, a female parasitoid wasp has to decide whether to learn positive or negative cues related to a host. The optimal female decision will depend on the fitness costs and benefits of learned stimuli. Reward quality is positively related to the rate of behavioral acquisition in processes such as associative learning. Wolbachia, an endosymbiotic bacterium, often plays an impressive role in the manipulation of its arthropod host's biology. Here we studied the responses of two natural Wolbachia infected/uninfected Trichogramma brassicae populations to theoretically high- and low- reward values during a conditioning process and the consequences of their responses in terms of memory duration. According to our results, uninfected wasps showed an attraction response to high value rewards, but showed aversive learning in response to low value rewards. Memory span of uninfected wasps after conditioning by low-value rewards was significantly shorter compared to high-value rewards. As our results revealed, responses to high quality hosts will bring more benefits (bigger size, increased fecundity and enhanced survival) compared to low-quality hosts for uninfected wasps. Infected wasps were attracted to conditioned stimuli with the same memory duration after conditioning by both types of hosts. This was linked to the fact that parasitoids emerging from both types of hosts present the same life-history traits. Therefore, these hosts represent the same quality reward for infected wasps. According to obtained results it can be concluded that Wolbachia manipulates the learning ability of its host resulting in the wasp responding to all reward values similarly.
... In recent years , several studies have investigated the effects of neonatal stress on behavior and stress resistance in animal and human models, and have found that prenatal stress can affect the emotional and cognitive ability of rat pups (Cabrera et al., 1999;Nishio et al., 2001), in addition Furthermore, rhesus monkeys raised in an enriched neonatal environment, have superior performance in orientation and motor activity, with fewer temperamental responses (such as fear) compared to rhesus raised in a less rich environment (Schneider et al., 1991;Bard et al., 2001). Tremblay (2002) suggested that some types of maternal care improve spatial learning and memory of the offspring by increasing hippocampal development. ...
... INTRODUCTION ulation by the hypothalamic-pituitary-adrenal (HPA) axis 23 (Vallee et al., 1997(Vallee et al., , 1999Dugovic et al., 1999;Koenig 24 et al., 2005; but see Behan et al., 2011). Early-life stress 25 also affects behavior, leading to alterations in activity 26 levels (Vallee et al., 1997;Miyagawa et al., 2011;27 Matrisciano et al., 2012), changes in depressive-like and 28 anxiety-like behaviors (Stohr et al., 1998;Bosch et al., 29 2006;Miyagawa et al., 2011;Morley-Fletcher et al., 30 2011) and affects performance in tasks that assess learn-31 ing and memory (Vallee et al., 1997(Vallee et al., , 1999Stohr et al., 32 1998; Lehmann et al., 2000;Nishio et al., 2001;33 Bustamante et al., 2010). Among other neurotransmitter 34 systems, the integrity of the serotonergic system is partic-35 ularly susceptible to early stress exposure (Holloway 36 et al., 2013). ...
Article
Chronic maternal stress during pregnancy can have long-term, detrimental consequences for the offspring. An understanding of the mechanisms responsible for mediating these effects is essential for devising therapeutic interventions. Here, we examined whether serotonin 1A receptor (5-HT1AR) mediates the effects of maternal stress on the behavioural outcomes of the offspring as adults. Heterozygous (HET) mouse dams were bred with HET males and were randomly assigned to stress or control groups. Pregnant dams in the stress group were exposed to a regime of chronic unpredictable stress from embryonic day 7 to 18. At two months of age, groups of male and female wildtype (WT), HET, and knockout (KO) offspring underwent a comprehensive behavioral test battery that included tests of social behaviour, memory, aggression, anxiety, sensorimotor information processing, and exploratory and risk assessment behaviours. Independent of genotype, prenatal stress resulted in a change in locomotor activity and fear memory in male mice and a change in prepulse inhibition in female animals. 5-HT1AR KO affected anxiety in male mice, and fear memory and prepulse inhibition in female mice. 5-HT1AR genotype moderated the effects of maternal prenatal stress exposure on social behaviour of male offspring and on activity levels of female offspring. Our findings indicate that 5-HT1A receptor availability can affect outcomes of the offspring resulting from maternal prenatal stress exposure, and that these effects are sex-specific.
... Interestingly, some researches held that male and female offspring responded differentially to maternal stress such as for gestation outcomes (preterm births, birth weight. . .) [22], emotional behavior and learning abilities of neonatal rats [23]. Noteworthy, some studies have shown that maternal stress during gestation can enhance the adverse effects on the development and behavior of fetuses and neonates induced by some elements like aluminium, arsenic, mercury or manganese [24][25][26][27][28][29]. ...
Article
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Today, due to technology development and aversive events of daily life, Human exposure to both radiofrequency and stress is unavoidable. This study investigated the co-exposure to repeated restraint stress and WiFi signal on cognitive function and oxidative stress in brain of male rats. Animals were divided into four groups: Control, WiFi-exposed, restrained and both WiFi-exposed and restrained groups. Each of WiFi exposure and restraint stress occurred 2 h (h)/day during 20 days. Subsequently, various tests were carried out for each group, such as anxiety in elevated plus maze, spatial learning abilities in the water maze, cerebral oxidative stress response and cholinesterase activity in brain and serum. Results showed that WiFi exposure and restraint stress, alone and especially if combined, induced an anxiety-like behavior without impairing spatial learning and memory abilities in rats. At cerebral level, we found an oxidative stress response triggered by WiFi and restraint, per se and especially when combined as well as WiFi-induced increase in acetylcholinesterase activity. Our results reveal that there is an impact of WiFi signal and restraint stress on the brain and cognitive processes especially in elevated plus maze task. In contrast, there are no synergistic effects between WiFi signal and restraint stress on the brain.
... Interestingly, some researches held that male and female offspring responded differentially to maternal stress such as for gestation outcomes (preterm births, birth weight. . .) [22], emotional behavior and learning abilities of neonatal rats [23]. Noteworthy, some studies have shown that maternal stress during gestation can enhance the adverse effects on the development and behavior of fetuses and neonates induced by some elements like aluminium, arsenic, mercury or manganese [24][25][26][27][28][29]. ...
Article
The present study was carried out to investigate the potential combined influence of maternal restraint stress (and 2.45 GHz WiFi signal exposure on postnatal development and behavior in the offspring of exposed rats. 24 pregnant albino Wistar rats were randomly assigned to four groups: Control, WiFi-exposed, restrained and both WiFi-exposed and restrained groups. Each of WiFi exposure and restraint occurred 2 h/day along gestation till parturition. The pups were evaluated for physical development and neuromotor maturation. Moreover, elevated plus maze test, open field activity and stationary beam test were also determined on postnatal days 28, 30 and 31, respectively. After behavioral tests, the rats were anesthetized and their brains were removed for biochemical analysis. Our main findings showed no detrimental effects on gestation progress and outcomes at delivery in all groups. Subsequently, WiFi and restraint, per se and mainly in concert altered physical development of pups with slight differences between genders. Behaviorally, the gestational WiFi irradiation, restraint and especially the associated treatment affected the neuromotor maturation mainly in male progeny. At adult age, we noticed anxiety, motor deficit and exploratory behavior impairment in male offspring co-exposed to WiFi radiation and restraint, and in female progeny subjected to three treatments. The biochemical investigation showed that, all three treatments produced global oxidative stress in brain of both sexes. As for serum biochemistry, phosphorus, magnesium, glucose, triglycerides and calcium levels were disrupted. Taken together, prenatal WiFi radiation and restraint, alone and combined, provoked several behavioral and biochemical impairments at both juvenile and adult age of the offspring.
... Prenatally stressed males exhibit impairments on learning-induced neurogenesis (Lemaire, et al., 2000), and reduced hippocampal long-term potentiation (LTP), together with increased long-term depression (LTD) (Yang, et al., 2006), which potentially correlates with the alterations reported on cognitive behavior. Prenatally stressed females, on the other hand, are more susceptible to a dysfunctional emotional behavior exhibiting an increase in anxiety and depressivelike behaviors (Nishio, et al., 2001, Weinstock, 2007, Zagron and Weinstock, 2006. Furthermore, prenatally stressed females exhibit a reduction in the number of hippocampal granule cells (Schmitz, et al., 2002). ...
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Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals’. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.
... In various species, the retention of memory ranges from a few seconds to several years (Rankin et al., 1990;Portavella et al., 2004;Giurfa, 2007;Giurfa & Sandoz, 2012;Bruck, 2013). This duration is determined by numerous factors such as the number of training sessions (Toppino & Bloom, 2002), diet (Suzuki et al., 1998;Petursdottir et al., 2008), aging (Gallagher & Rapp, 1997;Page & Peng, 2001;Schaie et al., 2004;Weiler et al., 2008;Bartolo et al., 2010), stress (Nishio et al., 2001;Shors, 2004), reward intensity and value (Adcock et al., 2006;Hoedjes et al., 2010;Kruidhof et al., 2012), or cold exposure (van Baaren et al., 2006). External biotic factors such as viruses, bacteria, and fungi can also affect the learning ability of animals. ...
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Several factors, such as cold exposure, aging, the number of experiences and viral infection, have been shown to affect learning ability in different organisms. Wolbachia has been found worldwide as an arthropod parasite/mutualist symbiont in a wide range of species, including insects. Differing effects have been identified on physiology and behavior by Wolbachia. However, the effect of Wolbachia infection on the learning ability of their host had never previously been studied. The current study carried out to compare learning ability and memory duration in two strains of the parasitoid Trichogramma brassicae: one uninfected and one infected by Wolbachia. Both strains were able to associate the novel odors with the reward of an oviposition into a host egg. However, the percentage of females that responded to the experimental design and displayed an ability to learn in these conditions was higher in the uninfected strain. Memory duration was longer in uninfected wasps (23.8 h and 21.4 h after conditioning with peppermint and lemon, respectively) than in infected wasps (18.9 h and 16.2 h after conditioning with peppermint and lemon, respectively). Memory retention increased in response to the number of conditioning sessions in both strains, but memory retention was always shorter in the infected wasps than in the uninfected ones. Wolbachia infection may select for reduced memory retention because shorter memory induces infected wasps to disperse in new environments and avoid competition with uninfected wasps by forgetting cues related to previously visited environments, thus increasing transmission of Wolbachia in new environments. This article is protected by copyright. All rights reserved.
... Like Thompson (1957), some have applied stress across the entire gestation period (Weinstock et al., 1992, Weinstock et al., 1998. A small sampling has also restricted stress to the middle of the gestation period (Nishio et al., 2001, Koenig et al., 2005. Still, the predominant stress regimen has been across the last week (beginning on GD 14 or 15) of prenatal development (Weinstock, 2008). ...
Article
The importance of neurodevelopmental events in utero is well established. When these processes are disrupted, the consequences are severe and long-lasting. Such is the case when prenatal growth overlaps with maternal stress (prenatal stress [PS]). Preclinical studies suggest that links between PS and emotional irregularities are a consequence of altered development of the limbic system. Because limbic circuitry also mediates reward processes, it is no surprise that PS facilitates rats??? susceptibility to drugs. Nevertheless, most of these studies have been performed with males. How PS affects the drug response of females, which is already greater than that of males, is largely unknown. Here we used cocaine to test both sexes, with the hope of better understanding whether PS alters the sexually-dimorphic risk of drug use escalating to problematic proportions. In our first study, we used in vivo microdialysis to determine if PS alters a sex difference in striatal functioning of rats that are drug na??ve. In concordance with previous work, males without a history of PS expressed higher steady-state concentrations of dopamine than their female littermates. No sex difference was evident, however, in rats that did have a history of PS. PS lowered extracellular concentrations in males, but had no effect in females. Next we tested whether PS has sex-dependent effects on the response to cocaine, as predicted by results with microdialysis. Interestingly, PS facilitated the acquisition of drug taking exclusively in males, but augmented psychomotor sensitization selectively in females. Because self-administration and sensitization are both considered reliable indicators of drug susceptibility, it was unclear (in the context of addiction) whether PS was a greater risk factor for males or females. To resolve this uncertainty, we utilized a longer self-administration test regimen to more accurately model the extent of drug use observed in human addicts. After weeks of testing, we found that PS sex-dependently increased the number of addiction-like traits expressed by females. Although work at the clinical level is still needed for support, this suggests that PS places female drug users at increased risk of becoming addicted, perhaps by augmenting drug-associated neuroplasticity.
... Behavioral changes associated with perinatal stress have been extensively studied. However, studies have found contradictory results for every behavior, including learning and memory (Vallee et al., 1997;Stohr et al., 1998;Vallee et al., 1999;Lehmann et al., 2000;Nishio et al., 2001;Bustamante et al., 2010), exploratory behavior (Vallee et al., 1997;Miyagawa et al., 2011;Matrisciano et al., 2012), and depressive-and anxiety-like behaviors (Stohr et al., 1998;Bosch et al., 2006;Miyagawa et al., 2011;Morley-Fletcher et al., 2011). ...
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Methods: C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non-stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal (P) day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress, perinatal Flx, prenatal stress and Flx, or neither stress nor Flx, went through a comprehensive behavioral test battery. At the end of the battery brain derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. Results: Maternal behaviour was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behaviour, prenatal maternal stress decreased aggressive behaviour. Interestingly, the combined effects of stress and Flx normalized aggressive behaviour. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behaviour in male offspring. Prenatal stress led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress nor fluoxetine altered offspring performance in tests of cognitive abilities, memory, sensorimotor information processing, and risk assessment behaviours. These results demonstrate that maternal exposure to stress and Flx have a number of sustained effects on the male offspring.
... In addition, the prenatal environment has been shown to differentially affect male and female offspring. Prenatal stress produces sex specific alterations in spatial learning, object recognition, delayed alteration, and passive avoidance (Bowman et al., 2004;Szuran et al., 2007;Weinstock, 2001;Koenig, Elmer, Shepard, Lee, Mayo, Joy, et al., 2005) and evidence suggests that males may be more impaired by gestational stress than females (Mueller & Bale, 2007;Szuran et al., 2007;Weinstock, 2001;Koenig et al., 2005;Nishio et al., 2001). Since exercise can be a type of stressor, future research should determine if maternal exercise during pregnancy affects cognition in males and females differently. ...
Article
Substantial research has established that exercise can improve mental health and cognitive function in both human and non-human animals. Exercise has been shown to improve learning and memory in both adult and juvenile animals, with larger and more durable effects associated with exercising during development. Exercise during the gestational period has also been shown to improve cognition in the offspring. Several recent studies indicate that the offspring of mothers that exercised during pregnancy exhibit improved learning and memory and decreased anxiety-like behaviors. These behavioral changes are accompanied by increased neurogenesis, neurotrophic factor expression, and neuronal activity in the offspring. This review summarizes the current literature regarding the effects of maternal exercise in rodents and presents avenues for future research to reveal the biological mechanism(s) through which maternal exercise changes the brain and behavior of the offspring.
... Acute stress disrupts both spatial and recognition memory as assessed by a number of behavioral tasks including radial arm maze, water maze, radial arm water maze, and spontaneous recognition memory tests (Cazakoff et al., 2010). Nishio et al. demonstrated that prenatal stress exposure obviously influences the learning abilities in the offspring (Nishio et al., 2001). Prenatally stressed rats spend a shorter time in the open arms of plus maze; demonstrating a higher degree of anxiety (Murmu et al., 2006). ...
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Background: It is believed that cognitive processing is easily disturbed by incompatible environmental stimulations. Many studies have shown that prenatal stress affects fetal brain development. The aim of this study was to evaluate the effect of noise pollution exposure during conception period on neural activity of hippocampus CA1 area in male rat offspring. Methods: Four groups of rats includ ing a control group with natural pregnancy and without any stress and three groups of pregnant rats exposed to daily noise stress (inte nsity >95 dB, between 8 A.M - 2 P.M) with durations of 1, 2 and 4 hour (s) in the last week of pregnancy were included in the study. Then, in male offsprings of these groups, fEPSP resulted from Schaffer collateral neurons of CA1 were recorded and evaluated in baseline state and after LTP induction with tetanic stimulation. Results: Our results showed that prenatal exposure to traffic noise pollution at 3rd gestational week, reduce s amplitude (P<0.0001) and slope of baseline synaptic activity in hippocampus CA1 area (P<0.0001) and furthermore interfere s in hippocampal LTP in comparison with control group. The serum level of corticostrone in the two stressed groups (2 and 4 hours) of rats in comparison to the control showed significant increase. But, prenatal exposure to 1- hour noise pollution caused no significant difference in serum corticostrone level. Conclusions: Based on the obtained results, daily exposure to noise pollution in the third trimester of pregnancy for 1, 2 and 4 hour (s), attenuates fEPSP features of hippocampus CA1 area pyramidal neurons of offsprings.
... In another study, gestational restraint stress had no effect on object recognition memory and improved performance of female offspring in a radial arm maze, eliminating the gender differences seen in controls (Bowman, MacLusky, Sarmiento, Frankfurt, Gordon, & Luine, 2004). In contrast to those findings, however, other studies have reported that prenatal stress retarded the acquisition of reversal learning (Weller, Glaubman, Yehuda, Caspy, & Ben-Uria, 1988) and of spatial learning in a water maze (Lemaire, Koehl, Le Moal, & Abrous, 2000;Nishio, Kasuga, Ushijima, & Harada, 2001;Szuran, Pliska, Pokorny, & Welzl, 2000). ...
Chapter
This chapter examines the interactions of environmental stress with lead (Pb). These interactions are relevant in the understanding of the role of Pb as a contributor to human disease and dysfunction and also in the understanding of the mechanisms of neurotoxicity and other target organ toxicities associated with Pb. The greatest elevations in blood lead levels (BLLs) now occur in low socioeconomic status (SES) populations, and the same populations are hypothesized to experience the highest levels of environmental stress and presumed chronic elevations of glucocorticoids. Both Pb and low SES stress are also associated with similar behavioral deficits in terms of cognitive dysfunction. Biological plausibility for an interaction between Pb and stress derives from the fact that both act on the mesocorticolimbic dopamine system of the brain. In the mesocorticolimbic system, nucleus accumbens (NAC) receives dopaminergic input from neurons in the ventral tegmental area, as well as glutamatergic projections, both NMDA and AMPA/kainite‐mediated, from the septo‐hippocampal system and from the prefrontal cortex (PFC). Pb exposure also impacts mesocorticolimbic systems.
... Previous findings have demonstrated that PNS or maternal exposure to glucocorticoids may affect the responsivity of the hypothalamic-pituitary-adrenal (HPA) axis and can induce cognitive deficits in offspring (10,16,17,(19)(20)(21)(22). Cognitive deficits that result from disrupted hippocampal anatomy and impaired function of the HPA axis are also typically observed in patients with schizophrenia (23,24). ...
Article
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Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single‑nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia.
... In other studies, while prenatal stress lowered the ability to learn in male offspring, the same stress did not affect female offspring. It even increased their learning performance [52][53][54], which is in consistent with our result. Gonadal hormones have been suggested to contribute to the observed differences. ...
Article
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Objectives Limited evidence is available regarding the association between prenatal job strain and infant neurodevelopment. Most studies used stress indicators other than job strain to explain the relationship between prenatal maternal stress and child development. The objective of this study was to investigate the association between maternal job strain during pregnancy and neurodevelopment in infancy. Methods Mothers and Children’s Environmental Health (MOCEH) study, an on-going prospective birth cohort study, has been conducted in South Korea since 2006. Job strain during pregnancy was measured using Korean version of Job Content Questionnaire (JCQ). Infant neurodevelopment was assessed using Korean Bayley Scale of Infant Development II (K-BSID-II) at 6 and 12 months of age. A total of 343 mother-child pairs that completed JCQ and K-BSID-II more than once were included. Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) defined in the K-BSID-II were used as outcome variables. Results Compared to infants from mothers with low job strain, significant (p < 0.05) decreases in PDI were found in infants from mothers with active and passive job at 6 months of age. After stratification by infant sex, boys in the high strain group had a lower MDI score than boys in the low job strain group at 12 months. On the other hand, girls in the high strain and active groups had higher MDI scores than girls in the low job strain group at 12 months. PDI at 12 months also showed different results by sex. Boys in the high strain and passive job groups had lower PDI scores than boys in the low job strain group. However, such difference was not observed in girls. Conclusions The findings of this study suggest that prenatal job strain affects infant neurodevelopment in a gender-dependent manner.
... Glucocorticoids (GCs) are important transcription factors belonging to the nuclear receptor superfamily which regulate the expression of a number of genes (Carson-Jurica, Schrader, & O'Malley, 1990). During prenatal stress, as a consequence of the disruption of the placental barrier, the fetus is massively exposed to the negative effects of GCs (Mairesse et al., 2007) leading to hypothalamic-pituitary-adrenal (HPA) axis developmental alterations (Abe et al., 2007), neuronal plasticity loss in the hippocampus (Hayashi et al., 1998;Zhu et al., 2004) and functional and cognitive deficits (Lemaire, Koehl, Le Moal, & Abrous, 2000;Nishio, Kasuga, Ushijima, & Harada, 2001). ...
Article
Prenatal stress (PNS) is a risk factor for the development of neuropsychiatric disorders. This study was aimed at assessing, in a rodent model, changes in gene expression profiles and behavioral output as a result of PNS, during periadolescence, a critical developmental period for the onset of psychopathology. Social behavior was studied in a standardized social interaction paradigm and the expression of Brain-Derived Neurotrophic Factor (Bdnf), a marker of neuronal plasticity, and of inhibitory and excitatory mechanisms (Na(+) -K(+) -2Cl(-) and K(+) -Cl(-) cotransporters ratio, NKCC1/KCC2) was analyzed. Results indicate that PNS reduced Bdnf transcripts while increasing the NKCC1/KCC2 ratio, primarily in the hippocampus. In the prefrontal cortex, changes in Bdnf were found to be gender-dependent. These effects were accompanied by reduced levels of affiliative and investigative social behaviors. Interestingly, interaction with non-stressed subjects was able to improve sociality in PNS rats suggesting that the social environment could be exploited for therapeutic intervention. © 2015 Wiley Periodicals, Inc. Dev Psychobiol. © 2015 Wiley Periodicals, Inc.
... Absence of effect and both increase and decrease of state of anxiety are described in the literature. For instance, in non-pregnant females, a 65 dB white noise increase the state of anxiety [36] and no effect was shown in pregnant females subjected to a 77 dB noise of 800 Hz [37]. In addition, white noise exposure increased anxiety behavior in adult male rats [38] and decreased it in fifteen-day-old male pups [39]. ...
Article
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In the present study we evaluated the effects of chronic exposure to sounds at 22 kHz during pregnancy on the central serotonergic and behavioral parameters in Wistar rat dams after the suckling period and on their male rat offspring. In addition, we also assessed the effects of an acute 22 kHz sound, associated with the chronic intrauterine exposure, on the emotional responses of adult offspring. The primary hypothesis was that experiencing 22 kHz stimuli during an early stage of development would interfere with brain serotonergic parameters and, later, with the adult rat's defensive responses. The corollary question was whether a 22 kHz sound exposure would differentially affect inhibitory avoidance and escape responses and central serotonergic parameters. Female rats were divided into four groups: non-pregnant control; non-pregnant chronic exposure; pregnant control; and pregnant chronic exposure. Male offspring were divided into four groups: chronic intrauterine sound exposure; acute sound exposure in adulthood; chronic intra-uterine exposure with acute exposure in adulthood; and no exposure. Chronic sound exposure af-26 fected inhibitory avoidance and serotonergic parameters in female rats. For offspring, there was an interaction between chronic and acute sound exposure effects on inhibitory avoidance response but not on escape response. There were significant effects of chronic intrauterine exposure on serotonin turnover in the hippocampus and PFC of females. For offspring, the turnover was increased by chronic exposure only in PFC, and in amygdala it was increased by acute exposure. These results illuminate the potential of an early acoustic sound exposure for causing central serotonergic and emotional behavioral changes that can persist into later periods of life.
... Spatial working memory and attention skills are predicted by maternal exposure to life events during pregnancy. Research in rodents provides direct evidence of a causal role of maternal stress during pregnancy (MSDP) in spatial learning and working memory deficits in offspring [1][2][3]. MSDP induces alterations in the orbitofrontal and anterior cingulate cortices, two brain regions that are shared by attention and working memory [4,5]. In humans, questions remain about the involvement of MSDP in both attention and working memory. ...
... Acute stress disrupts both spatial and recognition memory as assessed by a number of behavioral tasks including radial arm maze, water maze, radial arm water maze, and spontaneous recognition memory tests (Cazakoff et al., 2010). Nishio et al. demonstrated that prenatal stress exposure obviously influences the learning abilities in the offspring (Nishio et al., 2001). Prenatally stressed rats spend a shorter time in the open arms of plus maze; demonstrating a higher degree of anxiety (Murmu et al., 2006). ...
Article
Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2 and 4 hours. The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison to the non-pregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals. © 2014 Wiley Periodicals, Inc.
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The overarching aim of prenatal diagnostic imaging is the timely identification of congenital anomalies to inform parents and guide clinical decision-making in terms of prognosis, fetal intervention, mode of delivery, or termination of pregnancy. This chapter discusses the timing, safety, and general informational gains of fetal US and MR.
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Accumulation of environmental contaminants like heavy metals in food is a major source of human exposure. Their adverse effects are well documented, but there is little information about the health problems arising from their exposure during critical periods of life of development. The aim of the chapter was to examine the possible neurotoxic effects after exposure of pregnant females and lactating mothers and their pups to different heavy metals in order to evaluate the possible dysfunctions.KeywordsNeurotoxic effectsExposureFoodHeavy metalsAccumulationPregnant femalesLactating mothers
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Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.
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p>Prenatal stress (PS) induced by immobilization produces defi ciencies in spatial learning and information retrieval. These defi ciencies seem to be larger in males than in females, and have been explained as an effect of fetal exposure to high concentrations of maternal corticosterone during stress response. However, the effects of PS have only been assessed at a single time point and/or sex. In this work, the effect of PS on spatial learning and memory induced by immersion in cold water was evaluated in young and adult rats of both sexes. PS was induced during gestational days 15 through 21. Corticosterone in dams, body weight, corticosterone, learning and memory were assessed in male and female offspring at one, two, and three months of postnatal life. Results showed that escape latencies of PS rats of both sexes were longer as compared to those of control groups and that the number of platformsite crossovers and time spent in the platform quadrant were lower in the PS animals as compared to the control groups. Corticosterone levels were higher in PS females and males compared with controls. The body weight was decreased only in PS males of one month of age. These results show that PS by immersion in cold water alters learning and memory processes in the offspring, regardless of sex or age, since the effects are similar in females and males during youth and adulthood. These behavioral effects are related to high serum corticosterone.</p
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Significance Maternal stress during gestation causes numerous effects on infant physiology that extend well into adulthood. We contribute to the ongoing debate on whether these effects are adaptive outcomes or merely the product of energetic constraints by presenting an integrated hypothesis that predicts the diversity of observed maternal effects on offspring growth, incorporating both theoretical explanations into one coherent framework. Empirical tests of this hypothesis across mammals suggest that the timing of the stressor during gestation and a simultaneous consideration of maternal investment and adaptive growth plasticity effects are crucial for a full comprehension of prenatal stress effects on offspring growth. The results support an adaptive life history perspective on maternal effects that is relevant for evolutionary biology, medicine, and psychology.
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In the last decade much progress has been made in research using animal models of developmental psychopathology. The field has moved from the demonstration of long-term impacts of early adversity on behavioral and physiological development and the role of genetic risks for vulnerability, to including transgenerational transmission of stress-induced phenotypes through epigenetic modifications. Additional and critical paradigm shifts have also taken place, including increased focus on ecologically and ethologically valid animal models, research on resilience, the adolescent transition as a period of brain and behavioral reorganization, and sex differences. In this chapter we review recent literature using rodent and nonhuman primate animal models that examines the biological mechanisms through which the early environment programs neurobehavioral, cognitive, and physiological development. We discuss the evolutionary role of this plasticity on behavioral development, as it has an adaptive value in changing environments. Because of maternal care's critical role in early environment, we focus on models that study the effects of mother–infant relationship disruption and dissect the mechanisms by which maternal care regulates the development of brain circuits that control emotional and social behaviors of relevance for developmental psychopathology. Finally, we discuss developmental sensitive/critical periods as windows of opportunity for plastic adaptation of developing organisms to the environment that, if taken too far—as in the case of early traumatic experiences such as childhood maltreatment—lead to maladaptive developmental trajectories (psychopathology, pathophysiology). Animal models of early life adversity are paramount to understand the basic mechanisms and principles that translate early experience into developmental outcomes in our own species.
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While effects of gestational, neonatal or adolescent stress on psychological alterations in progeny have been extensively studied, much less is known regarding the effects of adult pre-gestational life events on offspring behavior. Although full siblings often display behavioral differences, whether the different parental life events prior to different pregnancies contribute to these behavioral differences among siblings is worth studying. In this study, male and female adult mice were restrained for 60 days before mating with unstressed or stressed partners. F1 offspring were examined for anxiety or mated to generate F2. Both F1 females and males from restrained mothers and/or fathers showed significantly reduced anxiety and serum cortisol and increased mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor compared to control offspring from unstressed parents. Similar behavioral and molecular changes were also observed in F2 females and males. Although restraint of adolescent mice reduced anxiety in F1 of both sexes, social instability of them increased anxiety predominantly in F1 females. Thus, adult pre-gestational restraint reduced offspring's anxiety across generations; different stressors on parents may cause different phenotypes in offspring; individual behaviors can depend on adult life experiences of parents.
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This chapter reviews the literature on the development of event memory and the brain system that underlies it. It describes what is known about the explicit memory system and its development, as well as areas in which more could be understood about the development of the system. It reviews the literature on effects of stress on the development of the explicit memory system, and proposes ways in which timing and plasticity could play a role in long-term effects of stress on the brain basis of memory.
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Biologists have known for decades that many traits involved in competition for mates or other resources and that influence mate choice are exaggerated, and their expression is influenced by the individuals' ability to tolerate a variety of environmental and social stressors. Evolution of Vulnerability applies this concept of heightened sensitivity to humans for a host of physical, social, psychological, cognitive, and brain traits. By reframing the issue entirely, renowned evolutionary psychologist David C. Geary demonstrates this principle can be used to identify children, adolescents, or populations at risk for poor long-term outcomes and identify specific traits in each sex and at different points in development that are most easily disrupted by exposure to stressors.
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We tested the effect of early life stress (ELS) - 24 h maternal deprivation at postnatal day 3 - on cognitive performance and hippocampal structure in 12-17 weeks old female rats. Behavioral performance was examined in: the elevated plus maze, as an index for general anxiety; the rodent Iowa gambling test, probing reward-based decision making; and the object recognition and object-in-location task, to assess non-stressful contextual memory performance. We further determined hippocampal dentate gyrus volume and cell density as well as adult proliferation and neurogenesis rates. Half of the rats was treated with the glucocorticoid receptor antagonist mifepristone during a critical pre-pubertal developmental window (postnatal days 26-28), in an attempt to ameliorate the potentially adverse behavioral consequences of ELS. Neither maternal deprivation nor treatment with the glucocorticoid antagonist affected behavioral performance of the females in any of the tasks. Also, dentate gyrus structure, proliferation and neurogenesis were not different between the groups. The lack of structural differences and a behavioral phenotype in non-stressful hippocampus dependent learning tasks fits with the lack of phenotype generally reported after ELS in female but less so in male rodents. As evident from an extensive literature review, female and male animals appear to respond more similarly to early life adversity when tested in anxiety-related tasks. This agrees with recent findings in humans suggesting that females may be relatively resilient to the structural / hippocampal effects of childhood maltreatment, but not to the anxiety and mood-related psychopathology for which childhood maltreatment is considered a risk factor. Copyright © 2015. Published by Elsevier Ltd.
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A growing body of evidence suggests that prenatal stress increases the vulnerability to neuropsychiatric disorders. On the other hand, the ability to adapt to stress is an important defensive function of a living body, and disturbance of this stress adaptability may be related, at least in part, to the pathophysiology of stress-related psychiatric disorders. The aim of the present study was to clarify the relationship between exposure to prenatal stress and the ability to adapt to stress in mice. Naive and prenatally stressed mice were exposed to repeated restraint stress for 60min/day for 7 days. After the final exposure to restraint stress, the emotionality of mice was evaluated in terms of exploratory activity, i.e., total distance moved as well as the number and duration of rearing and head-dipping behaviors, using an automatic hole-board apparatus. A single exposure to restraint stress for 60min induced a decrease in head-dipping behavior in the hole-board test. This acute emotional stress response disappeared in naive mice that had been exposed to repeated restraint stress for 60min/day for 7 days, which confirmed the development of stress adaptation. In contrast, prenatally stressed mice did not develop this stress adaptation, and still showed a decrease in head-dipping behavior after the repeated exposure to restraint stress. Biochemical studies showed that the rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase, was increased in raphe obtained from stress-adapted mice. In contrast, a decrease in tryptophan hydroxylase was observed in stress-maladaptive mice. In addition, the transcription factor Lmx1b, which is essential for differentiation and the maintenance of normal functions in central 5-HT neurons, was decreased in the embryonic hindbrain and adult raphe of prenatally stressed mice. These findings suggest that exposure to excessive prenatal stress may induce a vulnerability to stress and disrupt the development of 5-HT neurons.
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The pharmacotherapy of anxiety is in a state of flux at present. Critical issues that have emerged in the past decade are the risk/benefit ratio of the traditional anxiolytics, the benzodiazepines, the efficacy of newer agents such as buspirone, and the re-emergence of classical antidepressants such as the tricyclics and monoamine oxydase inhibitors (MAOIs) as anxiolytics. Additionally, the operationalization of diagnosis according to schema such as the DSM III-R has opened up a debate about the optimal treatments for different syndromes, even though not all psychiatrists agree that such diagnostic distinctions are valid (Ashcroft et al., 1987; Gelder, 1989).
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The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as "healthy" or "asphyxiated" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated.
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The effects of maternal hyperexcitability on the fetus were studied in 17 baboons. In the period of agitation, induced by stressful stimulus such as exposure to bright light or by clamping of the toe, the mother exhibited an increase in arterial blood pressure and, in some instances, arrhythmia. These changes were accompanied by an increased uterine activity and reduced uterine blood flow, and resulted in a decrease in heart rate and arterial oxygenation in all fetuses. Fetal recovery was prompt after maternal agitation was terminated, either by removal of the stimulus or by sedation with pentobarbital or nitrous oxide. This sedation also prevented a decrease in uterine blood flow when stress was repeated.
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Diazepam, a potent minor tranquilizer, binds with high affinity to a specific benzodiazepine receptor that occurs exclusively in the central nervous system. The receptor is mainly localized in the synaptic membrane fraction. Binding to the receptor is stereospecific. Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency.
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Over the past decade, a variety of serotonin (5-hydroxytryptamine, 5-HT) receptor/binding sites have been identified. These include 5-HT1, 5-HT2, and 5-HT3 sites. The 5-HT1 sites have been further divided into 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D and 5-HT1E sites. It would be of interest to identify those pharmacological effects that are specifically mediated by a particular population of 5-HT sites and, indeed, attempts have been made to do this almost since the initial discovery of multiple populations of sites. Unfortunately, much of the early work made use of serotonergic agents that are now known to be somewhat less selective than originally suspected. Nevertheless, there is ample information in the literature suggesting that site-selective serotonergic agents may ultimately lead (and, in some cases, has already led) to the development of therapeutically-useful agents. The present review examines the pharmacological effects that are thought to be related to the individual types of 5-HT sites and provides some clinical implications for agents that act at these sites.
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The effects of learning memory tasks on activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the frontal cortex (FC), hippocampus (HC) and cerebellum of aged rat brains were studied in comparison with those of young adult rats. Aged rats were significantly inferior than young adult rats in both active avoidance (two-way shuttle box) and water-filled multiple T-maze learning. ChAT activity in the FC of aged rats was significantly increased after 5 days of training in an active-avoidance learning task. ChAT activity in the HC of aged rats was also significantly increased after 6 days of training in a water-filled multiple T-maze. These changes did not occur in young adult rats after either 2 or 5 days of active avoidance training, or in aged rats after 10 days of training, both of which were after the maximum level of learning of active avoidance task had been attained. AChE activity was significantly lower in the FC and HC of nontrained aged rats when compared with that of nontrained young adult rats. The reduced activity of AChE in both brain regions of nontrained aged rats rose to almost the same level as that in young adult rats in nontrained and trained states in an active avoidance task. From these findings, it is hypothesized that the task-dependent elevation in the activities of the central nervous system (CNS) cholinergic marker enzymes in trained aged rats may be compensatory changes to keep a relevant level of neurotransmission in the face of specific motor and/or cognitive insults.
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Pregnant ICR mice were immersed in water at 42 or 43 degrees C for 10 min once or twice daily on days 12 through 15 of gestation and the postnatal development of their offspring was observed. Postnatal weight gain of the offspring and their brain weight at 11 weeks of age were smaller than the values for control animals. As compared with controls, prenatally heated mice were less active in an open field and learned slower in a water-filled multiple T-maze and in a shuttle box. Thus, prenatal brief hyperthermia in mice was shown to suppress the body and brain growth during the postnatal period and adversely affect their emotionality and learning capacity.
Article
Male rats were exposed to prenatal or postnatal stress, or both. The prenatally stressed males showed low levels of male copulatory behavior and high rates of female lordotic responding. Postnatal stress had no effect. The modifications are attributed to stress-mediated alterations in the ratio of adrenal to gonadal androgens during critical stages of sexual differentiation. Specifically, it appears that stress causes an increase in the weak adrenal androgen, androstenedione, from the maternal or fetal adrenal cortices, or from both, and a concurrent decrease in the potent gonadal androgen, testosterone.
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Testosterone and androstenedione were identified in pools of testicular and adrenal venous blood of the rat by chromatographic mobility as free steroids and as derivatives and by retention time in gas-liquid chromatography. A double isotope derivative method was developed for the estimation of testosterone in blood using 14C steroids as internal standards and acetic anhydride-1-3H as indicator; androstenedione was reduced with NaBH4 and measured as testosterone. The nonspecific blanks for testosterone and androstenedione were 0.006 ± 0.006 (sd) and 0.10 ± 0.09 (sd) μg/100ml blood, respectively. The testosterone concentration in the testicular venous blood of untreated rats was 4.2 ± 0.56 (se) μg/100 ml and of ether-saline treated animals was 1.4 ± 0.42 (se) μg/100 ml; the significant difference in the testosterone concentration between these 2 groups (p < 0.01) suggests that the stress of ether administration lowered endogenous gonadotropin production. Both testosterone and androstenedione secretion incre...
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Out of 865 homosexual males who were registered by venerologists in 6 districts of the GDR highly significantly more homosexuals were born during the stressful war and early postwar period of the Second World War, i.e. between 1941 and 1947 (with a maximum of relative frequency in 1944-1945), than in the years before or after this critical period. This finding suggests that stressful prenatal (or perinatal) events may represent an aetiogenetic factor for homosexuality in human males.
Article
Previous research indicates that the offspring of dams exposed to stress during late gestation show altered hypothalamic-pituitary-adrenal (HPA) responses to stress. However, the results are inconsistent and a review of the literature suggests that the effects may differ depending upon the gender of the offspring. In the present study, we measured plasma adrenocorticotropin (ACTH) and corticosterone (B) levels prior to, and at 0, 20, 40 and 70 min following restraint stress in catheterized adult male and female offspring of dams stressed in the last week of gestation (i.e. days 15-19 of gestation). Prenatal stress significantly increased both plasma ACTH and B levels in response to restraint, but only in females; male offspring were largely unaffected. In addition, plasma corticosteroid-binding globulin (CBG) levels were significantly increased in prenatally-stressed females, but not in males. Despite these differences in plasma CBG, estimated free B levels following restraint were also significantly elevated in prenatally-stressed females. We then examined glucocorticoid receptor binding in a variety of forebrain structures. Prenatal stress had no effect on glucocorticoid receptor density in the hypothalamus or hippocampus in either males or females. Differences in glucocorticoid receptor density across groups were observed in the septum, frontal cortex, and amygdala. However, the pattern of observed differences across the groups was not consistent with the pattern of hormonal differences. In summary, the effect of prenatal stress on HPA function is substantially more marked in females than in males. Interestingly, a similar pattern of effects on HPA activity has been reported for prenatal alcohol exposure.
Article
Mild prenatal stress affects the serotonergic system in the hippocampus of rat offspring. Pregnant rats were daily exposed to mild stress treatments (consisting of crowding and saline injection) during days 15 to 21 of pregnancy. Their offspring were assessed by a series of biochemical, histological and behavioral tests. On 35 days after birth, 5-hydroxytryptamine (5-HT) level was decreased by 17% (P < 0.05), whereas 5-hydroxyindolacetic acid (5-HIAA) level was increased by 18% (P < 0.05) in the offspring of prenatally stressed rats. The metabolic rate (5-HIAA/5-HT) was increased by 49% (P < 0.01). Synaptic density in the hippocampus of prenatally stressed offspring was also decreased by 32% (P < 0.0001) on postnatal day 35. There was no significant group difference in the spatial learning acquisition test of the Morris water maze; however, in the reversal task, prenatally stressed 5-week old rats spent more time than control animals searching for the platform of the pool. Escape latency in the cued test showed no significant difference. Together with data in our previous studies, that have shown 5-HT to facilitate synapse formation and maintenance in the central nervous system, synaptic loss is suggested to occur in relation to changes of 5-HT system in the hippocampus of prenatally stressed offspring. This may be associated with reported changes in behavior and learning ability in prenatally stressed offspring.
Article
Fibers of the global projection system ramify tremendously and distribute in the diverse region of the brain. Biogenic amines in the global projection system have been shown to facilitate formation and maintenance of synapses in the developing and adult brain. In terms of serotonin 5-HT2A receptor was shown to mediate the function of serotonin. We raised specific antibodies against 5-HT2A receptor protein. Virtually all the neurons in the cerebral cortex expressed 5-HT2A receptor. By using the function of biogenic amines to facilitate synapse formation and maintenance a novel approach can be developed in the neuroscience. That is to perturb biogenic amines, to change synaptic density, and to examine changes in the ability of learning and memory. Removing serotonin and acetylcholine for a week, at the maximum 58% of synapses are decreased in the hippocampus. The animals losing synapses spent a longer latency compared to intact animals in Morris water maze. The level of biogenic amines in the developing brain has been known to decrease tremendously by genetic diseases such as phenylketonuria, Down syndrome and autism as well as environmental factors such as nutrition and stress. In those situations synapses in the brain are suggested to be decreased. Synaptic mechanism for mental retardation and developmental disability by the cascade appears to contribute for understanding pathophysiology and a new therapy.