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ABSTRACT: In adult rodents, endocannabinoids (eCBs) regulate fast glucocorticoid (GC) feedback in the HPA axis, acting as retrograde messengers that bind to cannabinoid receptors (CB1R) and inhibit glutamate release from presynaptic CRH neurons in the PVN. During the first two weeks of life, rat pups exhibit significant CRH and ACTH responses to stress although the adrenal GC output remains reduced. At the same time, pups also display increased sensitivity to glucocorticoid (GC) feedback, but it is unclear whether eCBs play a role in mediating fast GC feedback in neonatal life. In our studies, we examined the role of eCBs in rapid suppression of anoxia-induced ACTH release and determined whether eCB action could be modulated by levels of circulating glucocorticoids present at the time of stress. PND8 pups were subjected to 3 min anoxia with AM251, a CB1R blocker, injected 30min prior to stress onset. The effects of either metyrapone (a steroidogenic 11beta-hydroxylase blocker) or methylprednisolone (a synthetic GC) pretreatment on AM251 effect and the stress response were evaluated. Treatment with AM251 before stress onset tended to increase overall ACTH and CORT secretion, and also delayed the return to baseline ACTH. The AM251 effect on ACTH in PND8 pups was lost in metyrapone-treated pups, who exhibited high basal and stimulated ACTH release and no CORT response to stress. Methylprednisolone suppressed ACTH stress responses although AM251 still delayed restoration of ACTH levels to baseline. This suggests that the eCB effect on ACTH secretion in neonates is most evident when there is a dynamic fluctuation of corticosterone levels. Interestingly, AM251 increased basal and stimulated corticosterone secretion in all treatments including metyrapone, suggestive of a direct action of CB1R blockade on adrenal steroidogenesis.
Neuroscience 11/2012; · 3.38 Impact Factor
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ABSTRACT: Stress during the prenatal and early postnatal periods (perinatal stress, PS) is known to impact offspring cognitive, behavioral, and physical development, but effects on skeletal growth are not clear. Our objective was to analyze effects of variable, mild, daily PS exposure on adult offspring long bone length. Twelve pregnant rat dams were randomly assigned to receive variable stress from gestational days 14-21 (Prenatal group), postpartum days 2-9 (Postnatal), both periods (Pre-Post), or no stress (Control). Differences in adult offspring tibia and femur length were analyzed among treatment groups. Mean tibia length differed among groups for males (P = 0.016) and females (P = 0.009), and differences for femur length approached significance for males (P = 0.051). Long bone length was shorter among PS-exposed offspring, especially those exposed to postnatal stress (Postnatal and Pre-Post groups). Results persisted when controlling for nose-tail length. These differences might reflect early stunting that is maintained in adulthood, or delayed growth among PS-exposed offspring. This study suggests that PS results in shorter long bones in adulthood, independently of effects on overall body size. Stunting and growth retardation are major global health burdens. Our study adds to a growing body of evidence suggesting that PS is a risk factor for poor linear growth. Am J Phys Anthropol 149:307-311, 2012. © 2012 Wiley Periodicals, Inc.
American Journal of Physical Anthropology 07/2012; 149(2):307-11. · 2.82 Impact Factor
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ABSTRACT: Stress is a known precipitant for metabolic and neurological diseases, with sensitive periods identified across the developmental continuum from conception to old age. However, the effects of stress may vary depending on the point or points along the developmental trajectory when adversity strikes. Past research has emphasized the consequences of stress on fully developed physiological systems in the brain and periphery, but more recent studies have explored the impact of stress on systems at different stages of maturation, with differential effects being revealed. This review provides an overview of the diverse effects of stress at critical developmental stages and the potential outcomes that may be associated with experiencing environmental adversity during ontogeny.
Stress (Amsterdam, Netherlands) 09/2011; 14(5):475-80. · 3.21 Impact Factor
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ABSTRACT: The frequency of adverse cardiovascular events is greater in the morning compared to its 24-hour average. A circadian variation in the regulation of the cardiovascular system could contribute to this increased cardiovascular risk in the morning. Indeed, circadian rhythms have been shown for a wide array of physiological processes. Using an ultradian sleep-wake cycle (USW) procedure, we sought to determine how heart rate (HR) and heart rate variability (HRV) correlate with the well-characterized circadian rhythms of cortisol and melatonin secretion. Specific HRV components, namely the low frequency (LF) power, high frequency (HF) power, and the LF:HF ratio can be used as markers of the autonomic modulation of the heart. Cross-correlation between HRV parameters and hormonal rhythms demonstrated that mean RR interval is significantly phase-advanced relative to salivary cortisol and urinary 6-sulfatoxy-melatonin (UaMt6s). Parasympathetic modulation of the heart (HF power) was phase-advanced relative to cortisol, but was in-phase with UaMt6s levels. Maximal correlation of the sympathovagal balance (the LF:HF ratio) had no significant lag compared to cortisol secretion and UaMt6s excretion. The protective effect of the parasympathetic nervous system at night, combined with the putative risk associated with the sympathetic nervous system peaking in the morning, could be associated with the increased cardiovascular risk observed in the morning hours.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2011; 2011:681-2.
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Claire-Dominique Walker
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ABSTRACT: For half a century, Seymour Levine's pioneering work on the interactions between mother and infant have helped us understand the critical early factors that shape physiology and behavior in the adult offspring. The work from my laboratory described in this review was based on many experiments by Levine and coworkers demonstrating that the quantity and quality of maternal milk and of maternal-infant contact influence different aspects of the hypothalamus-pituitary-adrenal (HPA) activity in the neonate. We have extended this work by showing that maternal high-fat feeding during the prenatal and lactational period blunts stress responsiveness in neonatal pups, in part mediated by increased circulating leptin levels in the offspring. The blunting of stress responses during this specific neonatal period might be beneficial to prevent the negative effects of exaggerated glucocorticoid secretion on the developing brain. In line with Levine's previous work, we found that maternal licking of the pups reduced stress responsiveness and inflammation in pups subjected to modest repeated pain during the first weeks of life and that it also blunted adult sensitivity to thermal pain. These studies have important implications for human infants as mechanisms aimed at reducing stress responsiveness can be considered protective to the developing brain from exaggerated and untimely neuroendocrine and sympathetic stimulation. Non-invasive interventions targeted at maternal nutrition and maternal care are relatively easy to implement and might have a significant effect on the health outcome of the offspring, particularly in a vulnerable population of term and pre-term babies.
Developmental Psychobiology 11/2010; 52(7):638-50. · 2.98 Impact Factor
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ABSTRACT: Pharmacological blockade of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), produces CB(1) receptor (CB(1)R)-mediated analgesic, anxiolytic-like and antidepressant-like effects in murids. Using behavioral and electrophysiological approaches, we have characterized the emotional phenotype and serotonergic (5-HT) activity of mice lacking the FAAH gene in comparison to their wild type counterparts, and their response to a challenge of the CB(1)R antagonist, rimonabant. FAAH null-mutant (FAAH(-/-)) mice exhibited reduced immobility in the forced swim and tail suspension tests, predictive of antidepressant activity, which was attenuated by rimonabant. FAAH(-/-) mice showed an increase in the duration of open arm visits in the elevated plus maze, and a decrease in thigmotaxis and an increase in exploratory rearing displayed in the open field, indicating anxiolytic-like effects that were reversed by rimonabant. Rimonabant also prolonged the initiation of feeding in the novelty-suppressed feeding test. Electrophysiological recordings revealed a marked 34.68% increase in dorsal raphe 5-HT neural firing that was reversed by rimonabant in a subset of neurons exhibiting high firing rates (33.15% mean decrease). The response of the prefrontocortical pyramidal cells to the 5-HT(2A/2C) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI) revealed desensitized 5-HT(2A/2C) receptors, likely linked to the observed anxiolytic-like behaviors. The hippocampal pyramidal response to the 5-HT(1A) antagonist, WAY-100635, indicates enhanced tonus on the hippocampal 5-HT(1A) heteroreceptors, a hallmark of antidepressant-like action. Together, these results suggest that FAAH genetic deletion enhances anxiolytic-like and antidepressant-like effects, paralleled by altered 5-HT transmission and postsynaptic 5-HT(1A) and 5-HT(2A/2C) receptor function.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 09/2010; 35(10):2083-100. · 6.99 Impact Factor
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ABSTRACT: The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression, bipolar disorder (BD), and in the offspring of parents with major depression. Less is known about the offspring of parents with BD (FH+). The present project provides follow-up to a previous study showing that the adolescent (mean age 16.7 years) FH+ offspring had higher salivary cortisol levels than the offspring of parents with no mental disorder (FH-) throughout the day in their natural environment, and that girls had higher cortisol levels than boys (Ellenbogen MA, Hodgins S, Walker C-D, Adam S, Couture S. Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 2006; 31: 1164-1180). The goal of the present study was to determine whether FH+ offspring, approximately two years later, continued to exhibit elevated cortisol levels relative to FH- offspring during two weeks of daily sampling.
The present study examined salivary cortisol levels in 24 (18.3 +/- 2.6 years) FH+ and 22 (18.0 +/- 2.3 years) FH- offspring who are part of the same longitudinal cohort as the previous study. Saliva was collected at 1300 h and 1500 h in the natural environment of the offspring during 14 consecutive days.
Multilevel modelling analyses indicated that FH+ offspring had higher afternoon levels of cortisol in their natural environment than FH- offspring, but group differences in slope and gender differences were not found.
The FH+ offspring exhibited increased daytime secretion of cortisol that, at the level of the group, persisted into late adolescence and young adulthood. Perhaps this change in HPA functioning is associated with an increased vulnerability for the development of an affective disorder.
Bipolar Disorders 02/2010; 12(1):77-86. · 5.29 Impact Factor
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ABSTRACT: Children with Autism Syndrome Disorders (ASDs) exhibit social, communicative, and behavioral deficits. We know that human interaction with dogs, which is thought to serve as a social catalyst, results in a decrease of cortisol levels in healthy adults. Introducing service dogs to children with ASD is an attractive idea that has received growing attention in recent decades. However, no study has measured the physiological impact of service dogs on these children. Therefore, the goal of our study was to assess the effects of service dogs on the basal salivary cortisol secretion of children with ASD. We measured the salivary cortisol levels of 42 children with ASD in three experimental conditions; prior to and during the introduction of a service dog to their family, and after a short period during which the dog was removed from their family. We compared average cortisol levels and Cortisol Awakening Response (CAR) before and during the introduction of the dog to the family and after its withdrawal. We found that the introduction of service dogs translated into a statistically significant diminished CAR. Before the introduction of service dogs, we measured a 58% increase in morning cortisol after awakening, which diminished to 10% when service dogs were present. The increase in morning cortisol jumped back to 48% once the dogs were removed from the families (p<0.05). However, service dogs did not have an effect on the children's average diurnal cortisol levels. These results show that the CAR of children with ASD is sensitive to the presence of service dogs, which lends support to the potential behavioral benefits of service dogs for children with autism.
Psychoneuroendocrinology 02/2010; 35(8):1187-93. · 5.81 Impact Factor
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ABSTRACT: Endocannabinoids (eCBs) are products of phospholipid (PL)-derived arachidonic acid (AA) that regulate hypothalamus-pituitary-adrenal axis activity. We hypothesized that differences in the quality and quantity of maternal dietary fat would modulate the PL AA content in the neonatal brain affecting stress responsiveness via differences in eCB production and activity in stress-activated brain areas. Pregnant rats were fed a 5% [control (C)] or 30% fat [high fat (HF)] diet rich in either n-6 (HF-n-6) or n-3 (HF-n-3) fat during the last week of gestation and lactation. Postnatal d 10 offspring were tested for metabolic hormones, AA (n-6) and eCB brain content, and hormonal effects of eCB receptor antagonism (AM251, 1 or 3 mg/kg ip) on stress responses. Like maternal diet, milk from HF-n-3 mothers had a reduced n-6/n-3 fat ratio compared with that of C and HF-n-6 mothers. Hypothalamic and hippocampal levels of PL AA were diet specific, reflecting the maternal milk and dietary n-6/n-3 ratio, with HF-n-3 offspring displaying reduced AA content relative to C and HF-n-6 offspring. Plasma corticosterone and insulin were elevated in HF-fed pups, whereas leptin was increased only in HF-n-6 pups. Basal eCB concentrations were also diet and brain region specific. In C pups, eCB receptor antagonist pretreatment increased stress-induced ACTH secretion, but not in the HF groups. Stress-induced corticosterone secretion was not sensitive to AM251 treatment in HF-n-3 pups. Thus, the nature of preweaning dietary fat differentially influences neonatal metabolic hormones, brain PL AA levels, and eCB, with functional consequences on hypothalamus-pituitary-adrenal axis modulation in developing rat pups.
Endocrinology 02/2010; 151(4):1685-94. · 4.46 Impact Factor
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ABSTRACT: OBJECTIVES:
The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression, bipolar disorder (BD), and in the offspring of parents with major depression. Less is known about the offspring of parents with BD (FH+). The present project provides follow-up to a previous study showing that the adolescent (mean age 16.7 years) FH+ offspring had higher salivary cortisol levels than the offspring of parents with no mental disorder (FH-) throughout the day in their natural environment, and that girls had higher cortisol levels than boys (Ellenbogen MA, Hodgins S, Walker C-D, Adam S, Couture S. Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 2006; 31: 1164-1180). The goal of the present study was to determine whether FH+ offspring, approximately two years later, continued to exhibit elevated cortisol levels relative to FH- offspring during two weeks of daily sampling.
METHODS:
The present study examined salivary cortisol levels in 24 (18.3 +/- 2.6 years) FH+ and 22 (18.0 +/- 2.3 years) FH- offspring who are part of the same longitudinal cohort as the previous study. Saliva was collected at 1300 h and 1500 h in the natural environment of the offspring during 14 consecutive days.
RESULTS:
Multilevel modelling analyses indicated that FH+ offspring had higher afternoon levels of cortisol in their natural environment than FH- offspring, but group differences in slope and gender differences were not found.
CONCLUSIONS:
The FH+ offspring exhibited increased daytime secretion of cortisol that, at the level of the group, persisted into late adolescence and young adulthood. Perhaps this change in HPA functioning is associated with an increased vulnerability for the development of an affective disorder.
Bipolar Disorders 02/2010; 12(1-1):77-86. · 5.29 Impact Factor
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ABSTRACT: Repeated pain during brain development can have long-term consequences in both humans and animals. We previously showed that maternal care provided to pups experiencing pain reduced adult pain sensitivity. This study tested whether sensory stimulation was responsible for this effect. Rat pups were either mother-reared controls (MR-CON) or artificially reared (AR) with minimal (AR-MIN) or maximal (AR-MAX) stimulation provided daily. In each rearing condition, pups were either uninjected or injected from postnatal day (PND) 4 to 14 with saline (0.9%) or formalin (0.2-0.4%). Pain behavior and paw inflammation were scored. Thermal sensitivity and responses to formalin were tested in adulthood (PND 70). AR neonates, irrespective of sensory stimulation received, exhibited a pain response (p < 0.001), even with a mild formalin dose. Maternal rearing reduced inflammation during the second week of life compared with AR pups (p < 0.05). Early pain exposure did not modify adult pain sensitivity. However, rearing altered adult pain sensitivity such that uninjected MR-CON rats had lower pain sensitivities than uninjected AR rats (p < 0.05). This suggests that the beneficial effects of maternal rearing can be obliterated if additional stimulation/stress occurs during the early neonatal period. In addition, this suggests that optimal level of maternal stimulation exists that determines adult pain sensitivity.
Pediatric Research 07/2009; 66(3):272-7. · 2.70 Impact Factor
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Sleep Medicine 02/2009; 10(8):935-6. · 3.40 Impact Factor
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ABSTRACT: Both undernutrition and overnutrition of the mother during pregnancy and lactation produce a syndrome of altered energy balance in the offspring and has long-lasting consequences on CNS systems regulating food intake, metabolism, and food reward. Homeostatic circulating factors like insulin, glucocorticoids, and leptin that are generally increased by exposure to high fat/high caloric diets constitute important signals in these processes. They trigger functional activation of specific intracellular cascades mediating cellular sensitivity, survival, and synaptic plasticity. Using a model whereby the late fetal and neonatal rat is exposed to increased high fat (HF) via HF feeding of the mother, we investigated the proximal (neonatal) and distal (adult) consequences on metabolism and hippocampal function in the offspring. Adult offspring of HF-fed mothers displayed several of the physiological and behavioral changes susceptible to leading to metabolic complications. These include elevated circulating concentrations of leptin and corticosterone, increased body weight gain and food intake, modest preference for fat-containing food types, as well as the onset of hypothalamic leptin resistance. In the hippocampus, HF-fed offspring or neonates treated with leptin show similar increases in neurogenesis and survival of newborn neurons. We identified some of the direct effects of leptin to increase synaptic proteins, N-methyl-d-aspartate (NMDA), and glucocorticoid receptors, and to reduce long-term potentiation (LTP) prior to weaning. While these studies have documented effects in animal models, concepts can easily be translated to human nutrition in order to help design better perinatal diets and nutritional preventive measures for mothers in a coordinated effort to curb the obesity trend.
Annals of the New York Academy of Sciences 12/2008; 1144:189-202. · 3.15 Impact Factor
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ABSTRACT: Both undernutrition and overnutrition of the mother during pregnancy and lactation produce a syndrome of altered energy balance in the offspring and has long-lasting consequences on CNS systems regulating food intake, metabolism, and food reward. Homeostatic circulating factors like insulin, glucocorticoids, and leptin that are generally increased by exposure to high fat/high caloric diets constitute important signals in these processes. They trigger functional activation of specific intracellular cascades mediating cellular sensitivity, survival, and synaptic plasticity. Using a model whereby the late fetal and neonatal rat is exposed to increased high fat (HF) via HF feeding of the mother, we investigated the proximal (neonatal) and distal (adult) consequences on metabolism and hippocampal function in the offspring. Adult offspring of HF-fed mothers displayed several of the physiological and behavioral changes susceptible to leading to metabolic complications. These include elevated circulating concentrations of leptin and corticosterone, increased body weight gain and food intake, modest preference for fat-containing food types, as well as the onset of hypothalamic leptin resistance. In the hippocampus, HF-fed offspring or neonates treated with leptin show similar increases in neurogenesis and survival of newborn neurons. We identified some of the direct effects of leptin to increase synaptic proteins, N-methyl-d-aspartate (NMDA), and glucocorticoid receptors, and to reduce long-term potentiation (LTP) prior to weaning. While these studies have documented effects in animal models, concepts can easily be translated to human nutrition in order to help design better perinatal diets and nutritional preventive measures for mothers in a coordinated effort to curb the obesity trend.
Annals of the New York Academy of Sciences 11/2008; 1144(1):189 - 202. · 3.15 Impact Factor
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ABSTRACT: Repeated pain during a critical period of development can have long-term behavioral and physiological consequences in both human and animals. We previously showed that rat mothers caring for pups subjected to mild pain in neonatal life increased pup licking and grooming behavior. Therefore, we tested whether naturally occurring variations in maternal behavior would modulate the effects of repeated mild inflammatory pain on behavioral responses to pain and stress in the adult male offspring. Rat pups were either uninjected (UI) or injected twice daily between PND3 and PND14 with either saline (0.9%) or formalin (0.2-0.4%) in the footpad of the hindpaw. Maternal behavior (pup licking and grooming) was recorded under basal conditions and after reunion with the litter post injection to determine maternal phenotype (High, Middle, Low licking). Adult offspring (PND60) were tested for their thermal sensitivity, inflammatory pain responses after formalin injection and neuroendocrine responses to formalin injection. Maternal phenotype significantly altered pain sensitivity after thermal stimulation, but not formalin injection. Offspring from the High licking mothers displayed increased withdrawal latencies compared to offspring from Low mothers, regardless of neonatal treatment. Pain responses after formalin injection were higher in offspring receiving formalin as neonates compared to saline-treated or uninjected rats, demonstrating a long lasting increased sensitivity to inflammatory pain. Neuroendocrine responses to pain stress were not affected by neonatal treatment. These data suggest that changes in maternal behavior can influence some modalities of pain sensitivity and that repeated mild inflammatory pain in neonatal period causes hypersensitivity to formalin in the adult offspring.
Pain 10/2008; 140(1):167-76. · 5.78 Impact Factor
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ABSTRACT: Maternal stress during pregnancy, particularly that combined with low socioeconomic status (SES), has been linked to an increased risk for impaired behavioural and emotional development and affective disorders in children. In animal models, acute periods of prenatal stress have profound effects on hypothalamo-pituitary-adrenal (HPA) function and behaviour. However, few studies have determined the impact of chronic exposure to stress in animal models. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on growth, locomotor behaviour and HPA axis function in juvenile guinea pig offspring. Pregnant guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestation and from postnatal day (pnd) 1 until weaning (pnd25). CMS mothers displayed increased basal salivary cortisol levels in the later stages of pregnancy compared to control mothers (p<0.05). The male offspring of CMS mothers had a lower bodyweight, which was maintained to weaning (p<0.01). In open-field testing, CMS male offspring showed a decrease in activity compared to controls (p<0.05). There was no effect of CMS on bodyweight or activity in female offspring. In contrast, both male and female offspring born to CMS mothers displayed increased (p<0.05) basal salivary cortisol at pnd25, but a blunted adrenocortical response to exposure to the novel open-field enclosure. In conclusion, CMS leads to modification of growth trajectory, locomotor activity and adrenocortical responses to stress in juvenile offspring. Further, males appear considerably more vulnerable to these effects than females.
Hormones and Behavior 09/2008; 54(4):514-20. · 3.87 Impact Factor
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ABSTRACT: Early environment can shape the development and function of the mesocorticolimbic dopamine (DA) system and represents a possible risk factor for adult pathologies. One critical variable in the early environment is nutrition, and exposure to high fat (HF) in adulthood is known to change this DA system.
We tested whether perinatal HF intake in rats could have long-term effects on DA function and behavior in adult offspring.
Rat dams were fed either a control (5% fat, CD) or high fat (30% fat, HF) diet during the last week of gestation and lactation, and adult offspring were tested (PND 56-90) after weaning on CD. Locomotor responses to acute and repeated doses of D: -amphetamine (AMP, 0.75 mg/kg bw) were determined as were indices of DA function in the ventral tegmental area (VTA), nucleus accumbens (NAc), and the prefrontal cortex (PFC).
Adult HF offspring displayed increased tyrosine hydroxylase expression in the VTA and NAc and significant increases in DA and DOPAC content in the NAc, suggesting an elevated DA tone in this target field. In the NAc, there were no significant changes in D1, D2 receptors, or DA transporter (DAT) levels between diet groups. Perinatal HF feeding reduced AMP-induced locomotion and behavioral sensitization to AMP, suggesting that early diet might have caused long-lasting desensitization of postsynaptic receptor mechanisms in the NAc.
Our results demonstrate that both synthetic activity in VTA neurons and the responsiveness of accumbens DA neurons is altered by maternal nutrition. These effects subside long after termination of exposure to the HF diet.
Psychopharmacologia 04/2008; 197(1):83-94. · 4.08 Impact Factor
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ABSTRACT: Skin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates.
Preterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU's in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results.
PIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852-9.889) versus 10.677 (95%CI 9.563-11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103-142) versus 193 seconds (95%CI 158-227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition.
Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis.
(Current Controlled Trials) ISRCTN63551708.
BMC Pediatrics 01/2008; 8:13. · 1.88 Impact Factor
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Claire-Dominique Walker
Endocrinology 10/2007; 148(9):4147-9. · 4.46 Impact Factor
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ABSTRACT: The high circulating levels of leptin in neonatal rodents do not seem to be regulating energy balance at this age, but rather may play an important role for brain development. We tested the hypothesis that high neonatal leptin levels modify hippocampal function and production of synaptic proteins with possible long-term consequences on long-term potentiation (LTP) in adulthood. We first showed that in postnatal day (PND) 10 neonates, acute leptin treatment functionally activated leptin receptors (ObR) in the CA1 and DG regions of the hippocampus through the induction of phosphoERK1/2, but not phosphoSTAT3 protein although both phospho-proteins were induced in the arcuate nucleus. We next examined whether chronic leptin administration (3 mg/kg BW, intraperitoneally) during the first 2 weeks of life (postnatal day, PND 2-14) produces a functional signal in the hippocampus that alters the expression of NMDA receptor subunits (NR1, NR2A, NR2B), synaptic proteins and LTP in the short and long-term. In PND 10 as in adults (PND 70) rats, chronic leptin treatment increased NR1 expression in the hippocampus while reducing NR2B protein levels. Elevated hippocampal concentrations of synapsin2A and synaptophysin were detected during leptin treatment on PND 10 suggesting increased neurotransmitter release. In adults, only SNAP-25 expression was increased after neonatal leptin treatment. LTP was reduced dramatically by leptin treatment in preweaning rats although the changes did not persist until adulthood. Elevated exposure to leptin during a critical period of neonatal hippocampal development might serve to enhance NMDA-dependent functions other than LTP and have important effects on synaptogenesis and neurotransmitter release.
Journal of Neuroscience Research 04/2007; 85(4):816-28. · 2.74 Impact Factor
