Prenatal Protein Malnutrition in Rats Alters the c-Fos Response of Neurons in the Anterior Cingulate and Medial Prefrontal Region to Behavioral Stress

Bates College, Льюистон, Maine, United States
Nutritional Neuroscience (Impact Factor: 2.27). 10/2004; 7(5-6):281-9. DOI: 10.1080/10284150400015573
Source: PubMed

ABSTRACT Prenatal protein malnutrition affects brain development and behavior despite dietary rehabilitation from birth. Behavioral alterations include abnormal responses to stressors. To explore what brain regions mediate this altered response, we used immunocytochemistry to c-Fos protein, a transcription factor marking neuronal activation. Controls (25% casein diet) and prenatally malnourished (6% casein) adult rats were subjected to 20min of restraint stress or were unstressed. Plasma corticosterone levels were monitored before and after stress. Paired comparisons of corticosterone levels confirmed that both groups showed a significant post-stress increase. Three hours after onset of stress, rats were perfused with paraformaldehyde. Brain sections were immuno-stained together for c-Fos. Since anterior cingulate and medial prefrontal cortex modulate stress responses, labeled neurons in this region were quantified using unbiased stereology. A 2-way ANOVA of neuron numbers demonstrated a strong effect of stress and a stress by nutrition interaction. Post-hoc comparisons showed that stress significantly increased the number of c-Fos labeled neurons in both nutrition groups. Within the stress condition, prenatally malnourished rats showed a significantly greater number of c-Fos positive neurons than well-nourished rats. These results suggest that neurons in anterior cingulate and medial prefrontal regions respond excessively to restraint stress in prenatally malnourished rats.

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    • "One possibility is that early childhood malnutrition affects personality development via direct impacts on the brain. Early protein malnutrition impacts both the prefrontal cortex and hippocampus (Lister et al., 2011; Rosene et al., 2004). A recent PET study suggested that increased neuroticism and extraversion on the NEO-PI-R were associated with changes in glucose metabolism specific to the orbitofrontal cortex and the insular cortex (Deckersbach et al., 2006 "
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    ABSTRACT: Background: Early childhood malnutrition is associated with cognitive and behavioral impairment during childhood and adolescence, but studies in adulthood are limited. Methods: Using the NEO-PI-R personality inventory, we compared personality profiles at 37-43 years of age (M 40.3 years, SD 1.9) of Barbadian adults who had experienced moderate-to-severe protein-energy malnutrition (PEM) in the first year of life (n = 77) with healthy controls, who were former classmates of the index cases and were matched for age, gender, and handedness in childhood (n = 57). The previously malnourished participants had been rehabilitated, with good health and nutrition documented up to 12 years of age, and study participants were followed longitudinally from childhood to 40 years. Group comparisons were adjusted for childhood and adolescent standard of living, with and without correcting for IQ. Results: At the broad domain or factor level, previously malnourished participants had higher scores on Neuroticism and lower scores on Extraversion, Openness, Agreeableness, and Conscientiousness than did the healthy controls. At the subdomain or facet level, previously malnourished participants reported more anxiety, vulnerability, shyness and lowered sociability, less intellectual curiosity, greater suspiciousness of others, a more egocentric than altruistic orientation, and a lowered sense of efficacy or competence. Conclusions: Malnutrition limited to the first year of life with good health and nutrition documented up to 12 years of age is associated with a significant overrepresentation of adult personality trait scores outside of the average range. This outcome has important implications for a variety of important life and mental health outcomes.
    Journal of Child Psychology and Psychiatry 03/2013; 54(8):911-919. DOI:10.1111/jcpp.12066 · 6.46 Impact Factor
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    • "Hypothetically, reduced glucocorticoid receptor expression in these sites would result in decreased negative feed-back control by glucocorticoids and thereby in increased HPA activity. This possibility is supported by studies reporting higher expression of hypothalamic corticotropin-releasing hormone (CRH) as well as greater plasma levels of adrenocorticotropin hormone (ACTH) and corticosterone/cortisol in rats and lambs that underwent different forms of prenatal undernutrition [7] [19] [22] [26] [34]. Epidemiologic studies have also associated low birth weight of babies, an index of intrauterine undernutrition , with increased basal plasma cortisol levels when adults [25]. "
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    ABSTRACT: Prenatal undernutrition is known to disturb the hypothalamo-pituitary-adrenal (HPA) axis, possibly through the programming of decreased expression of hypothalamic and pituitary glucocorticoid receptors. To test this hypothesis, we examined the corticosterone response to moderate subcutaneous (100 microg/kg) and intra-paraventricular (50 pmol, bilaterally) dexamethasone (DEX) challenges in normal eutrophic and prenatally undernourished young rats. Undernutrition was induced during fetal life by restricting the diet of pregnant mothers to 10 g daily, while mothers of eutrophic rats received the same diet ad libitum. At day 40 of postnatal life (i) undernourished rats showed increased plasma corticosterone concentration compared to normals; and (ii) subcutaneous and intra-paraventricular administrations of DEX led to reduced corticosterone levels in normal and undernourished animals, the effect of DEX (administered either peripherally or centrally) being significantly lower in the latter group. Results suggest that the low sensitivity of the HPA axis to DEX as well as the increased plasma corticosterone observed in prenatally undernourished rats could be due to the already reported glucocorticoid receptor underexpression found in the hypothalamus and pituitary of in utero undernourished animals, but alternative explanations involving central noradrenergic adaptive changes could also be possible.
    Neuroscience Letters 06/2007; 419(2):99-103. DOI:10.1016/j.neulet.2007.04.019 · 2.03 Impact Factor
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    • "The changes in the serotonergic system that we have reported in malnourished rats may reflect changes in the actions of glucocorticoids at the level of the raphé nuclei. Rosene et al. (2004) have reported, using the same period of restraint stress, that plasma corticosterone levels do not increase in malnourished animals while wellnourished animals show an expected increase in plasma corticosterone. This finding is again suggestive of a blunted stress response in malnourished animals. "
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    ABSTRACT: Prenatal protein malnutrition continues to be a significant problem in the world today. Exposure to prenatal protein malnutrition increases the risk of a number of neuropsychiatric disorders in adulthood including depression, schizophrenia and attentional deficit disorder. In the present experiment, we have examined the effects of stress on extracellular serotonin (5-HT) and dopamine in the medial prefrontal cortex and dorsal hippocampus of rats exposed in utero to protein malnutrition. The medial prefrontal cortex and dorsal hippocampus were chosen as two limbic forebrain regions involved in learning and memory, attention and the stress response. Extracellular 5-HT and dopamine were determined in the medial prefrontal cortex and dorsal hippocampus of adult male Sprague-Dawley rats using dual probe in vivo microdialysis. Basal extracellular 5-HT did not differ between malnourished and well-nourished controls in either the medial prefrontal cortex or the dorsal hippocampus. Basal extracellular dopamine was significantly decreased in the medial prefrontal cortex of malnourished animals. Restraint stress (20 m) produced a significant rise in extracellular dopamine in the medial prefrontal cortex of well-nourished rats but did not alter release in malnourished rats. In malnourished rats, stress produced an increase in 5-HT in the hippocampus, whereas stress produced a decrease in 5-HT in the hippocampus of well-nourished rats. These data demonstrate that prenatal protein malnutrition alters dopaminergic neurotransmission in the medial prefrontal cortex as well as alters the dopaminergic and serotonergic response to stress. These changes may provide part of the bases for alterations in malnourished animals' response to stress.
    Brain Research 06/2007; 1148(1):226-33. DOI:10.1016/j.brainres.2007.02.031 · 2.84 Impact Factor
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