Selective serotonin reuptake inhibitor treatment of early postnatal mice reverses their prenatal stress-induced brain dysfunction

Prenatal stress has long-lasting effects on cognitive function and on the hypothalamic-pituitary-adrenal response to stress. We previously reported that the serotonin concentration and synaptic density in the hippocampus were reduced following prenatal stress [Int J Dev Neurosci 16 (1998) 209]. Since serotonin plays a role in the formation and maintenance of synapses, we hypothesized that a neonatal reduction in hippocampal serotonin levels may lead to learning disabilities in prenatally stressed mice. To test this hypothesis, we treated prenatally stressed mice with a selective serotonin reuptake inhibitor in order to normalize their postnatal serotonin turnover levels. What we found was that the oral administration of a selective serotonin reuptake inhibitor to prenatally stressed mice during postnatal weeks 1-3 but not 6-8 normalized their corticosterone response to stress, serotonin turnover in the hippocampus, and density of dendritic spines and synapses in the hippocampal CA3 region. Concomitantly, such treatment partially restored their ability to learn spatial information.     

Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: differential regulation of specific exons by antidepressants and corticosterone

Earlier studies have implicated brain-derived neurotrophic factor in stress and in the mechanism of action of antidepressants. It has been shown that antidepressants upregulate, whereas corticosterone downregulates, brain-derived neurotrophic factor expression in rat brain. Whether various classes of antidepressants reverse corticosterone-mediated downregulation of brain-derived neurotrophic factor is unclear. Also not known is how antidepressants or corticosterone regulates brain-derived neurotrophic factor expression. To clarify this, we examined the effects of various classes of antidepressants and corticosterone, alone and in combination, on the mRNA expression of total brain-derived neurotrophic factor and of individual brain-derived neurotrophic factor exons, in rat brain. Normal or corticosterone pellet-implanted (100 mg, 21 days) rats were injected with different classes of antidepressants, fluoxetine, desipramine, or phenelzine, intraperitoneally for 21 days and killed 2 h after the last injection. mRNA expression of total brain-derived neurotrophic factor and of exons I-IV was measured in frontal cortex and hippocampus. Given to normal rats, fluoxetine increased total brain-derived neurotrophic factor mRNA only in hippocampus, whereas desipramine or phenelzine increased brain-derived neurotrophic factor mRNA in both frontal cortex and hippocampus. When specific exons were examined, desipramine increased expression of exons I and III in both brain areas, whereas phenelzine increased exon I in both frontal cortex and hippocampus but exon IV only in hippocampus. On the other hand, fluoxetine increased only exon II in hippocampus. Corticosterone treatment of normal rats decreased expression of total brain-derived neurotrophic factor mRNA in both brain areas, specifically decreasing exons II and IV. Treatment with desipramine or phenelzine of corticosterone pellet-implanted rats reversed the corticosterone-induced decrease in total brain-derived neurotrophic factor expression in both brain areas; however, fluoxetine reversed the decrease only partially in hippocampus. Interestingly, antidepressant treatment of corticosterone pellet-implanted rats increased only those specific exons that are increased during treatment of normal rats with each particular antidepressant. We found that although corticosterone and antidepressants both modulate brain-derived neurotrophic factor expression, and antidepressants reverse the corticosterone-induced brain-derived neurotrophic factor decrease, antidepressants and corticosterone differ in how they regulate the expression of brain-derived neurotrophic factor exon(s).     

Mild prenatal stress enhances learning performance in the non-adopted rat offspring

The present study was designed to investigate whether mild stress during pregnancy affects offspring behaviors, including learning performance. Prenatal stress was induced by short-lasting, mild restraint stress, which had previously been shown to facilitate the morphological development of fetal brain neurons. Adult offspring whose dams had been restrained in a small cage for 30min daily from gestation day 15 to 17 showed enhanced active avoidance and radial maze learning performance. In addition, the prenatally stressed rats showed weaker emotional responses than unstressed control, as indicated by decreases both in ambulation upon initial exposure to an open field and in Fos expression in the amygdala induced by physical stress. The observed effects of prenatal stress on learning performance and emotional behavior were attenuated by foster rearing by unstressed dams. Fos expression in the hypothalamic paraventricular nucleus following physical stress and corticosterone secretion during physical and psychological stress did not differ between the prenatally stressed and unstressed control rats. From these results we suggest that mild prenatal stress facilitates learning performance in the adult offspring. The enhancement of learning performance appears to be accompanied by reduced emotionality, but not by any apparent alterations in hypothalamic-pituitary-adrenal responses. In addition, the observation of differential behaviors in the adopted and non-adopted animals supports the notion that the postnatal environment modifies the behavioral effects of prenatal stress.     

Chronic corticosterone manipulations in mice affect brain cell proliferation rates, but only partly affect BDNF protein levels

We investigated whether the effects of corticosterone (CORT) on brain cell proliferation are mediated via its detrimental effect on brain-derived neurotrophic factor (BDNF). Using a [3H]thymidine tracer study, it was demonstrated that the cell proliferation rate in the neurogenic hippocampus and subventricular zone was increased in placebo-treated adrenalectomized (ADX) mice with low plasma corticosterone levels when compared with chronically CORT-treated ADX animals (25mg or 100mg sustained-release pellet). The cell proliferation rate of SHAM animals was in between the ADX-placebo group and ADX CORT-treated groups. BDNF protein contents in the hippocampus and subventricular zone were not different between the SHAM group and ADX-placebo group, although BDNF contents were decreased in the chronically CORT-treated ADX animals. Thus, other factors besides BDNF are involved in mediating CORT-induced changes in cell proliferation. Further, CORT manipulations did not affect caspase-3-like activity in any of the brain regions investigated, suggesting that caspase-3 is not involved in possible CORT-induced cellular losses.     

Neonatal handling and environmental enrichment increase the expression of GAP-43 in the hippocampus and promote cognitive abilities in prenatally stressed rat offspring

Neonatal handling and environmental enrichment have been used to aid the treatment and recovery of a diverse variety of brain dysfunctions. However, the underlying mechanism and the effects on cognitive function following neonatal handling and environmental enrichment are still unclear. In this study, we investigated GAP-43 protein levels in the hippocampus of prenatally stressed rat pups by Western blot on postnatal day (P) 10, P20 and P45. The cognitive ability of prenatally stressed rat pups was tested by using the Morris water maze on P45. GAP-43 protein levels were upregulated on P10 in the prenatal restraint stress (RS) group and the prenatal restraint stress plus neonatal handling and environmental enrichment (RE) group compared to the negative control (NC) group. However, the expression of GAP-43 in RS pups was lower on P20 and P45 than that in NC and RE pups. Exposure to prenatal stress prolonged average latency and total swim distance, but neonatal handling and environmental enrichment could reverse the change. Differences were also observed in the selection of search strategies. These results indicate that neonatal handling and environmental enrichment can improve the spatial learning and memory ability of prenatally stressed offspring, and the possible mechanism is the upregulation of GAP-43.     

Mild prenatal stress in rats is associated with enhanced conditioned fear

We tested the hypothesis that prenatal stress would enhance conditioned fear in adult rats. Pregnant Sprague-Dawley rats were stressed by exposure to a novel environment and subcutaneous injection of saline (0.1 ml 0.9% NaCl) at random times daily from Days 14 to 21 of pregnancy. When compared to adult control (CON) male rats from unmanipulated pregnancies, adult prenatally stressed (PS) male rats showed increased freezing behavior in response to acute footshock as well as increased freezing behavior the next day in the same context, without shock delivery. In another experiment, the gestational stressor was examined for elevations in corticosterone and ACTH. At gestational days (G)15, G17, G19 and G21, maternal and fetal plasma was collected. Analysis showed elevations in corticosterone and ACTH in the PS dams when compared to the CON dams. Additionally, increased corticosterone was found in the PS fetuses when compared to the CON fetuses. Finally, some CON and PS litters were examined for alterations in length of gestation, number of pups born, bodyweight on postnatal day (P)1 and anogenital distance on P1 and differences were not found. In conclusion, our data demonstrate that a mild stressor during gestation, sufficient to raise plasma corticosterone and ACTH, is associated with enhanced conditioned fear during adulthood.     

Differential patterns of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNA and protein levels in developing regions of rat brain

The present studies were undertaken to characterize the regional and temporal patterns of neurotrophin messenger RNA and protein levels for beta-nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the developing CNS. We have examined the levels of these neurotrophin messenger RNAs with ribonuclease protection assays and corresponding protein levels with enzyme-linked immunosorbent assays in the developing Long-Evans rat hippocampus, neocortex and cerebellum on postnatal days 1, 7, 14, 21, and 92. In addition, immunohistochemistry was used to localize the neurotrophins in these developing brain regions. Results indicated that in neocortex and hippocampus, messenger RNA for both nerve growth factor and brain-derived neurotrophic factor increased in an age-dependent manner, reaching a plateau by postnatal day 14. In the neocortex, nerve growth factor and brain-derived neurotrophic factor protein levels both peaked at postnatal day 14. In hippocampus, nerve growth factor protein peaked at postnatal day 7 while brain-derived neurotrophic factor peaked at postnatal day 14. In cerebellum, nerve growth factor messenger RNA levels were flat, while nerve growth factor protein peaked at postnatal day 7. Brain-derived neurotrophic factor messenger RNA increased in an age-dependent manner while the pattern for its protein levels was mixed. Neurotrophin-3 messeger RNA levels increased in an age-dependent manner in hippocampus, peaked at postnatal day14 in cerebellum, and no changes occurred in neocortex. Neurotrophin-3 protein was at its peak at postnatal day 1 and thereafter decreased at other postnatal days in all three brain regions. Results of neurotrophin immunohistochemistry often paralleled and complemented enzyme-linked immunosorbent assay data, demonstrating specific cell groups containing neurotrophin proteins in these regions. Within each region, patterns with regard to messenger RNA and respective protein levels for each neurotrophin were unique. No consistent relationship between patterns of neurotrophin messenger RNAs and their cognate proteins was observed between regions. The different regional patterns for neurotrophin messengerRNA and protein levels in each brain region indicate that messenger RNA studies of neurotrophin messenger RNA must be augmented by protein determination to fully characterize spatial and temporal neurotrophin distribution.     

Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice

Human and animal studies have implicated brain-derived neurotrophic factor (BDNF) in the etiology of psychiatric disorders. It is expressed in limbic regions of the brain associated with the regulation of emotionality during fetal development and in the adult animal. To further our understanding of the role of BDNF in the modulation of mood and to distinguish its prenatal and postnatal functions, we investigated and contrasted behavioral changes elicited by its depletion from fetal or postnatal brains of mice. Two corresponding lines of BDNF conditional knockout mice were subjected to a battery of behavioral tests assessing locomotor, depressive, aggressive and anxiety-related behaviors. We found that both lines of mutants were dramatically hyperactive during the light and dark cycles and hyperaggressive. They also exhibited a depression-like phenotype in the tail suspension test but not in the forced swim test. Interestingly, depletion of BDNF from the fetal brain had more pronounced effects on aggressive and depressive-like behaviors and led to deficits in 5-HT(2A) receptor content in the medial frontal cortex, highlighting the importance of this neurotrophin during development. We conclude that expression of BDNF both pre- and postnatally is essential for normal modulation of behavior by neural circuits in the adult animal.     

Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age

We examined whether prenatal psychological stress with little physical stress causes changes in the behavior and neurogenesis of the offspring of Sprague–Dawley rats at one month. Dams in the last trimester of gestation were psychologically stressed by placing them in a social communication box and shocking a rat on the other side of a transparent wall. They suffered little physical stress. Male and female offspring from the dams showed little change in an open field test at postnatal day (PND) 30. To evaluate neurogenesis in the brain, BrdU was intraperitoneally injected at PND 35 into offspring not used in the open field test. Immunohistochemical examinations of BrdU in their dorsal hippocampus at PNDs 42 and 112 revealed that the number of BrdU immunopositive cells in the offspring of prenatally stressed rats was significantly smaller than in the offspring of unstressed ones. These results together with our previous finding that prenatal psychological stress can alter specific behaviors suggest that prenatal psychological stress can suppress neurogenesis in the dorsal hippocampus of rats of both sexes at PND 35 even though impairment in the behavioral task has not yet appeared.     

Prenatal stress effects on exploratory activity and stress-induced analgesia in rats.

Pregnant rats were exposed three times daily to immobilization stress during gestational Days 15-19. The behavior of their offspring was compared with the behavior of offspring from unstressed control mothers. Although the stress procedure decreased the weight gain of mothers during pregnancy, it slightly but significantly increased the weight of their offspring at birth and at weaning. On postnatal Day 10, prenatally stressed pups returned to their home cage more quickly than did prenatally unstressed control pups during a nest odor discrimination task, but no differences between groups in the number of correct responses were found. On postnatal Days 70-72, prenatally stressed offspring showed increased exploratory activity in a complex tunnel maze compared with control offspring. On postnatal Day 80, analgesia induced by stress (swimming for 3 min in cold water) was determined (tail flick latency). The degree of stress-induced analgesia was smaller in prenatally stressed rats than in control rats. These data suggest that the effects of prenatal stress on behavior are most clearly discernable when such animals are confronted with a novel or stressful situation.     

Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain

Exposure of pregnant rats to stress results in offspring that exhibit abnormally fearful behavior and have elevated neuroendocrine responses to novelty and aversive stimuli. This study examined the effects of prenatal stress on plasma corticosterone, adrenal weight, defensive withdrawal behavior, and the density of receptors for corticotropin releasing factor (CRF) in the amygdala. Pregnant Sprague-Dawley rats were stressed by daily handling and saline injection (s.c., 0.9%, 0.1 mL) during the last week of gestation. Male offspring were studied at adulthood (60-120 days of age). Adrenal hypertrophy and increased plasma corticosterone were observed in the prenatally stressed offspring. Defensive withdrawal, an ethological measure of the conflict between exploratory behavior and retreat, was quantified in naive offspring, and in offspring exposed to restraint stress (2 h). Restraint stress increased defensive withdrawal in both control and prenatally stressed offspring. Both naive and restraint-stressed prenatally stressed offspring exhibited increased defensive withdrawal compared to control offspring. There was a significant interaction between prenatal stress and restraint stress, suggesting increased vulnerability of prenatally stressed offspring. The effects of restraint in the defensive withdrawal test were reduced by intracerebroventricular administration of the CRF antagonists, alpha-helical CRF9-41 (20 microg every hour) or D-phe(12), Nle(21, 38), C(alpha)-MeLeu(37)]-CRF((12-41)) (5 microg every hour) during the restraint period. The difference between control and prenatally stressed offspring was abolished by the CRF antagonists, suggesting that increased activation of CRF receptors may be a factor in the behavioral abnormalities of prenatally stressed rats. Measurement of CRF receptors in amygdala revealed a 2.5-fold increase in binding in prenatally stressed offspring. In light of previous work from this laboratory demonstrating increased content and release of CRF in amygdala from prenatally stressed offspring, the present study suggests that the increased fearfulness of prenatally stressed rats may be a consequence of increased activity of CRFergic systems in the amygdala.     

Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex

Stress-mediated loss of synaptogenesis in the hippocampus appears to play a role in depressive and mood disorders. However, little is known about the effect of stress/depression on the plasticity and survival of cortical neurons. In this report, we have examined whether chronic stress increases the vulnerability of neurons in the rat cortex. We have used a chronic unpredictable mild stress (CMS) as a rat model of depression. CMS (5 weeks treatment) produced anedonia and increased corticosterone levels. These effects were accompanied by a detectable increase in caspase-3 positive neurons in the cerebral cortex, suggesting apoptosis. Desipramine (DMI), a well known antidepressant, reversed the pro-apoptotic effect of CMS. These results suggest that antidepressants may reduce the pathological changes seen in stress-induced depressive disorders.     

Effects of Prenatal Stress on the Activity of an Enzyme Involved in Neurosteroid Synthesis During the “Critical Period” of Sexual Differentiation of the Brain in Male Rats

The effects of daily immobilization stress applied to female rats on days 15 to 18 of pregnancy on the activity of the enzyme 5α-reductase (isoform I), involved in the synthesis of brain neurosteroids were studied in male offspring. The results demonstrated a decrease in enzyme activity in the cerebral cortex and hypothalamus of male fetuses one day after the last session of stress, while enzyme activity was elevated in the cortex of neonates. Increases in 5α-reductase activity in the cortex, hippocampus, and hypothalamus were also seen in prenatally stressed males on day 5 of life. There were reductions in plasma testosterone and progesterone levels in experimental animals on day 19 of embryonic life and in neonatal rats, the blood progesterone level in prenatally stressed rats remaining decreased at age five days. The possible involvement of neurosteroids in the actions of prenatal stress on sexual differentiation of the brain is discussed. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 90, No. 10, pp. 1255–1261, October, 2004.     

Prenatal stress reduces the effectiveness of the neurosteroid 3 alpha,5 alpha-THP to block kainic-acid-induced seizures

The effects of prenatal stress on the ability of the 5 alpha-reduced progesterone metabolite and neurosteroid 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) to prevent seizures was examined. On gestational Day 18, pregnant rats were exposed to 20 min of restraint stress (prenatal stress condition) or no such stress (control condition). The adult, gonadectomized offspring exposed to the prenatal stress or control condition were administered 0.0, 4.0, or 8.0 mg/kg 3 alpha,5 alpha-THP 1 hr prior to testing for kainic-acid-induced (32 mg/kg SC) ictal activity. The rats exposed to prenatal stress tended to have more partial seizures and significantly more tonic clonic seizures that were of longer duration than the no prenatal stress rats. Four mg/kg 3 alpha,5 alpha-THP was sufficient to significantly reduce seizure duration of no prenatal stress females, compared to the 0.0 mg/kg dosage of 3 alpha,5 alpha-THP. Seizure duration was reduced in no prenatal stress females by a dose of 4 mg/kg 3 alpha,5 alpha-THP, whereas a dose of 8 mg/kg was required to obtain comparable seizure reduction in prenatally stressed females and males in both groups. There was attrition following kainic-acid testing; of the 18 animals in each group originally, 9 prenatally stressed males, 6 prenatally stressed females, 6 nonprenatally stressed males and 5 nonprenatally stressed females were able to be tested in the water maze and perfused. One week after seizures, there were no differences in the water maze performance of the remaining animals. There were fewer cresyl violet-stained neurons in the CA3 region of the hippocampus of prenatally stressed rats compared to the nonprenatally stressed rats. Basal plasma corticosterone was greater in prenatally stressed animals, but this was due to increases in females rather than males. Plasma 3 alpha,5 alpha-THP was not significantly different in prenatally stressed males and females compared to their no prenatal stress counterparts. These data suggest that the sensitivity to, or responsiveness of, 3 alpha,5 alpha-THP to prevent seizures is decreased after prenatal stress, particularly in females.     

Prenatal stress in rats: effects on plasma corticosterone, hippocampal glucocorticoid receptors, and maze performance

The present experiments were designed to investigate the effects of maternal stress on cognitive and endocrine parameters in the adult offspring. Pregnant rats were stressed daily during the last week of pregnancy (days 15-19) by restraint, and the performance of their offspring in the Morris water maze was recorded. Plasma corticosterone levels after swimming and the status of hippocampal glucocorticoid receptors (GRs) were determined. During acquisition of the task, prenatally stressed (PS) males - but not females - showed longer escape latencies than non-stressed controls when swimming in cold (10 degrees C) but not in warm (20 degrees C) water. This sex- and prenatal stress-specific difference was even more pronounced during reversal learning of the task. In contrast, PS females - but not males - had higher basal corticosterone levels and a lower density of hippocampal corticosteroid receptors than non-stressed controls. In all animals irrespective of treatment, swimming in the water maze causes an increase of corticosterone that was smaller on day 8 of swimming than on day 1. After swimming in cold water, the rise in corticosterone levels in females was steeper and returned faster to baseline values than after swimming in warm water. A similar pattern could be seen in PS females when compared to their non-stressed controls. The data suggest that prenatal stress impairs spatial learning in males but not in females. Basal and stress-induced increases in corticosterone levels, however, were altered in PS females and not in PS males; i.e., prenatal stress-induced changes in corticosterone secretion were not paralleled by prenatal stress-induced deficits in spatial learning.     

Prenatal stress produces sex differences in nest odor preference

Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non-stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner.     

Effects of prenatal stress on motor performance and anxiety behavior in Swiss mice

Stressor presence during the last weeks of gestation has been associated with behavioral disorders in later life. In this study we support further research on the long term effects of prenatal stress on Swiss mice descendant's behavior. Prenatal stress procedure consisted on restraining the dams under bright light for 45 min, three times per day from the 15th day of pregnancy, until birth. After weaning, offspring's motor performance and spontaneous exploratory behavior were measured by the tight-rope and T-maze tests, respectively. We also evaluated anxiety behavior using elevated plus maze test. We found that maternal stress improves the performance of the animals in the tight rope test and that this effect was sex and age dependent: prenatal stressed males obtained the best scores during the first month of life, while in females the same was achieved at the second month. Spontaneous exploratory behavior analysis revealed that it was elevated in prenatal stressed males and that this effect persisted on time. However, we did not find significant differences on this behavioral response among both females groups. Finally, differences on anxiety behavior were found only in females: prenatally stressed animals showed a higher proportion of entries into the open arms of a plus maze (reduced anxiety) compared to the control group. Our results show that prenatal stress modifies the normal behavior of the progeny: prenatal stressed animals have a better performance in the carried out test. These notably results suggest the existence of an adaptive response to prenatal stress.     

Effects of gestational stress and neonatal handling on pain,analgesia, and stress behavior of adult mice

Stressors presented during the late prenatal and early postnatal periods can have long-term effects on offspring behavior, due to the sensitive periods in the formation of brain circuitry associated with early development. This study investigated the long-term effects of prenatal (restraint during the last week of gestation) and postnatal (daily handling for 14 days postnatal) stress, alone and in combination, on adulthood pain behavior, analgesic responses to stress and morphine, and on behavioral indices of stress reactivity. We found that all of the adult responses measured were altered by perinatal manipulations. Nociceptive thresholds were increased by prenatal or by postnatal stress in males and females; application of both stressors in combination negated these effects. Elevations in morphine analgesia were also observed in animals undergoing either perinatal stressor, but not in those who received both stressors. Behavioral and analgesic responses to stress were consistent with previous observations of reduced stress responsiveness following neonatal handling, with some sex-specific findings. Male and female handled subjects exhibited decreases in stress behavior, and both groups of female handled subjects (regardless of prenatal stress [PS] condition) exhibited decreases in stress-induced analgesia (SIA). Males, on the other hand, exhibited decreases in SIA only if they were prenatally stressed (regardless of handling condition). Thus, prenatal and postnatal stressors have differing effects on the neural circuitry underlying pain, pain inhibition, and stress behavior.     

Long-Term Effects of Prenatal Stress on the Characteristics of Hippocampal Neurons in Rats with Different Excitability of the Nervous Systems

We studied the effects of prenatal emotional painful stress on numerical density of neurons and characteristics of heterochromatin in developing and mature hippocampus of rats with different excitability of the nervous systems. It was shown that prenatal stress reduces the numerical density of neurons in hippocampal CA3 fi eld in 24-day-old and adult (3 months) low excitable animals and chromocenter area in cells of developing hippocampus in embryos of both strains. The difference in chromocenter areas in offspring of stressed females was retained on postnatal day 24.