Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning.

The effects of physical activity on spatial memory performance and associated cholinergic function were examined in F344 rats. Cholinergic analysis included resting and depolarization-induced activation of high-affinity choline uptake and muscarinic receptor binding in the hippocampus, parietal cortex and frontal cortex. Rats that were physically trained, using chronic treadmill running, demonstrated significantly enhanced performance on the spatial learning task, both in second trial latency and first and second trial proximity ratio scores (P less than 0.002). Concomitant with enhanced behavioral performance were neurochemical changes of a reduction in hippocampal high-affinity choline uptake, an upregulation of muscarinic receptor density, and an increase in high-affinity choline uptake 24 h after spatial memory testing (P less than 0.05). Spatial memory tested rats demonstrated enhanced depolarization-induced activation of high-affinity choline uptake (P less than 0.001). Rats that were yoked for swim time to spatial memory tested rats did not show any spatial learning-induced alterations in high affinity choline uptake. These spatial learning- and physical activity-induced cholinergic alterations were observed only in the hippocampus, not in the parietal or frontal cortex. These data indicate that the chronic running-induced alterations in hippocampal high-affinity choline uptake and upregulation of muscarinic receptor density, in combination with enhancement of high-affinity choline uptake related to spatial learning, may contribute to the enhanced spatial learning performance of chronic-run rats.     

Prenatal nicotine exposure mouse model showing hyperactivity, reduced cingulate cortex volume, reduced dopamine turnover, and responsiveness to oral methylphenidate treatment

Cigarette smoking, nicotine replacement therapy, and smokeless tobacco use during pregnancy are associated with cognitive disabilities later in life in children exposed prenatally to nicotine. The disabilities include attention deficit hyperactivity disorder (ADHD) and conduct disorder. However, the structural and neurochemical bases of these cognitive deficits remain unclear. Using a mouse model we show that prenatal nicotine exposure produces hyperactivity, selective decreases in cingulate cortical volume, and radial thickness, as well as decreased dopamine turnover in the frontal cortex. The hyperactivity occurs in both male and female offspring and peaks during the "active" or dark phase of the light/dark cycle. These features of the mouse model closely parallel the human ADHD phenotype, whether or not the ADHD is associated with prenatal nicotine exposure. A single oral, but not intraperitoneal, administration of a therapeutic equivalent dose (0.75 mg/kg) of methylphenidate decreases the hyperactivity and increases the dopamine turnover in the frontal cortex of the prenatally nicotine exposed mice, once again paralleling the therapeutic effects of this compound in ADHD subjects. Collectively, our data suggest that the prenatal nicotine exposure mouse model has striking parallels to the ADHD phenotype not only in behavioral, neuroanatomical, and neurochemical features, but also with respect to responsiveness of the behavioral phenotype to methylphenidate treatment. The behavioral, neurochemical, and anatomical biomarkers in the mouse model could be valuable for evaluating new therapies for ADHD and mechanistic investigations into its etiology.     

Neurochemical changes in brain serotonin neurons in immature and adult offspring prenatally exposed to cocaine

The present study investigates the age-dependent effects of prenatal cocaine exposure on changes in the neurochemical and functional status of brain serotonin neurons. Pregnant rats were administered either saline or (−)cocaine HCl (15 mg/kg, subcutaneously), twice daily from gestational days 13 through 20. Neurochemical changes in frontal cortex, hypothalamus, hippocampus, striatum and midbrain of prepubescent and adult offspring were determined by measuring: (1) the content of serotonin (5-HT) and its major metabolite 5-hydroxyindolacetic acid (5-HIAA), and (2) the ability of the serotonin releasing drug p-chloroamphetamine (PCA) to reduce brain serotonin levels. Brain catecholamine content was determined in progeny for comparative purposes. Prior to maturation, prenatal exposure to cocaine did not alter basal levels of brain 5-HT or 5-HIAA in any brain region examined. However, in adult progeny prenatally exposed to cocaine, basal 5-HT content was significantly reduced in the frontal cortex (−32%) and hippocampus (−40%), suggesting maturation-dependent effects of prenatal cocaine exposure on brain 5-HT neurons. Consistent with the maturational onset of changes in 5-HT, striatal dopamine was significantly reduced (−10%) by prenatal exposure to cocaine only in adult offspring. Reductions in 5-HT in most brain regions, produced by pharmacological challenge with p-chloroamphetamine (PCA), were comparable in prenatal saline versus cocaine offspring. One notable exception was the markedly greater reduction (−40%) in 5-HT in the midbrain of immature offspring prenatally exposed to cocaine, suggesting alterations in midbrain 5-HT neurons prior to maturation. Overall, these data demonstrate prenatal cocaine exposure produces region-specific changes in 5-HT neurons in offspring with some deficits occurring only following maturation.     

咖啡因对小鼠空间学习记忆能力及有关脑区记忆相关蛋白CREB表达的影响

目的：研究咖啡因对小鼠空间学习记忆能力以及有关脑区记忆相关蛋白——环腺苷酸应答元件结合蛋白（CREB）表达的影响。方法：C57BL／6J小鼠45只随机分成3组：咖啡因小剂量组（10mg·kg^-1）、咖啡因大剂量组（50mg·kg^-1）及生理盐水对照组，均腹腔给药。采用Morris水迷宫评价空间记忆能力及Western blot检测CREB的表达量。结果：与大剂量组及生理盐水对照组相比，咖啡因小剂量组定位航行实验逃避潜伏期显著缩短；空间搜索实验穿越原平台位置的次数显著增多；海马组织CREB表达显著增加。结论小剂量咖啡因能够提高小鼠空间学习记忆能力，且增加海马区CREB的表达。     

Effects of prenatal alcohol exposure on brain-derived neurotrophic factor and its receptor tyrosine kinase B in offspring

Prenatal alcohol exposure produces many developmental defects in the central nervous system. The underlying molecular mechanism, however, has not been fully understood. The present study was undertaken to examine the effects of prenatal alcohol exposure on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) in offspring. The pregnant Sprague-Dawley rats received 1 or 3 g/kg of alcohol or an isocaloric solution by intragastric intubation once a day from gestational day (GD) 5 to GD 20. On postnatal day 7-8, pups were killed and the hippocampus, striatum, cortex, and cerebellum dissected out. Levels of BDNF mRNA and proteins, total TrkB proteins and receptor phosphorylation were measured. The results showed that prenatal alcohol exposure at the dose of 1 g/kg/day did not significantly affect BDNF protein levels in any region examined. However, administration of alcohol at the dose of 3 g/kg/day markedly reduced levels of BDNF protein and mRNA in the cortex and hippocampus of offspring. Western blotting showed that prenatal alcohol exposure at the dose of 3 g/kg/day also inhibited TrkB phosphorylation in the hippocampus although no changes in total TrkB protein levels were observed in any region examined. Our data suggest that prenatal alcohol exposure alters both presynaptic and postsynaptic BDNF function in certain brain areas of offspring. These alterations in BDNF function may contribute to the development of alcohol-related birth defects.     

Reversibility of changes in brain cholinergic receptors and acetylcholinesterase activity in rats following early life arsenic exposure

In view of the increasing incidences of arsenic induced health effects and the vulnerability of the developing brain to its toxic effects, studies have been carried out to investigate the mechanism of arsenic induced cholinergic alterations and understand if such changes are persistent or transient on withdrawal of arsenic exposure. Male rats were exposed to arsenic (2 mg/kg or 4 mg/kg body weight, p.o) from post-lactational day (PD)22 to PD59, and the effect on selected behavioral and neurochemical end points associated with cholinergic functions was assessed on PD60 and PD90. Decrease in the binding of muscarinic-cholinergic receptors in frontal cortex (26%, 43%) and hippocampus (21%, 34%) associated with reduced CHRM2 mRNA levels, acetylcholinesterase activity and expression of ChAT and PKC β-1 was observed in arsenic exposed rats on PD60 as compared to controls. Spatial learning and memory and muscle strength were affected following arsenic exposure in rats on PD60 and associated with arsenic induced cholinergic alterations. Enhanced oxidative stress associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins was distinct in both frontal cortex and hippocampus following arsenic exposure in rats on PD60. The cholinergic alterations and other neurochemical modifications were found to be linked with increased arsenic levels in frontal cortex (1.39, 3.90-fold) and hippocampus (3.23, 5.48-fold) on PD60. Although a trend of recovery was observed both in behavioral and neurochemical endpoints on withdrawal of arsenic exposure on PD90, the results indicate that continuous arsenic exposure may have detrimental effects.     

Prenatal exposure to cigarette smoke causes persistent changes in the oxidative balance and in DNA structural integrity in rats submitted to the animal model of schizophrenia

Epidemiological studies have indicated that prenatal exposure to environmental insults can bring an increased risk of schizophrenia. The objective of our study was to determine biochemical parameters in rats exposed to cigarette smoke (CS) in the prenatal period, evaluated in adult offspring submitted to animal model of schizophrenia induced by acute subanaesthetic doses of ketamine (5 mg/kg, 15 mg/kg and 25 mg/kg). Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day, daily for a period of 28 days. We evaluated the oxidative damage in lipid and protein in the rat brain, and DNA damage in the peripheral blood of male adult offspring rats. To determine oxidative damage in the lipids, we measured the formation of thiobarbituric acid reactive species (TBARS) and the oxidative damage to the proteins was assessed by the determination of carbonyl groups content. We also evaluated DNA damage using single-cell gel electrophoresis (comet assay). Our results showed that rats exposed to CS in the prenatal period presented a significant increase of the lipid peroxidation, protein oxidation and DNA damage in adult age. We can observe that the animals submitted at acute doses of ketamine also presented an increase of the lipid peroxidation and protein oxidation at different doses and structures. Finally, we suggest that exposure to CS during the prenatal period affects two essential cerebral processes during development: redox regulation and DNA integrity, evaluated in adult offspring. These effects can leads to several neurochemical changes similar to the pathophysiology of schizophrenia.     

Cholinergic Dysfunctions and Enhanced Oxidative Stress in the Neurobehavioral Toxicity of Lambda-Cyhalothrin in Developing Rats

This study is focused on understanding the mechanism of neurobehavioral toxicity of lambda-cyhalothrin, a new generation type II synthetic pyrethroid in developing rats following their exposure from post-lactational day (PLD)22 to PLD49 and investigate whether neurobehavioral alterations are transient or persistent. Post-lactational exposure to lambda-cyhalothrin (1.0 or 3.0?mg/kg body weight, p.o.) affected grip strength and learning activity in rats on PLD50 and the persistent impairment of grip strength and learning was observed at 15?days after withdrawal of exposure on PLD65. A decrease in the binding of muscarinic-cholinergic receptors in frontocortical, hippocampal, and cerebellar membranes associated with decreased expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus was observed following exposure to lambda-cyhalothrin on PLD50 and PLD65. Exposure to lambda-cyhalothrin was also found to increase the expression of growth-associated protein-43 in hippocampus of rats on PLD50 and PLD65 as compared to controls. A significant increase in lipid peroxidation and protein carbonyl levels and decreased levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase in brain regions of lambda-cyhalothrin exposed rats were distinctly observed indicating increased oxidative stress. Inhibition of ChAT and AChE activity may cause down-regulation of muscarinic-cholinergic receptors consequently impairing learning activity in developing rats exposed to lambda-cyhalothrin. The data further indicate that long-term exposure to lambda-cyhalothrin at low doses may be detrimental and changes in selected behavioral and neurochemical end points may persist if exposure to lambda-cyhalothrin continues.     

Effects of noise on high-affinity choline uptake in the frontal cortex and hippocampus of the rat are blocked by intracerebroventricular injection of corticotropin-releasing factor antagonist

Acute exposure (20 min) to loud noise (100 dB) decreased sodium-dependent high-affinity choline uptake activities in the frontal cortex and hippocampus of the rat. These effects were blocked by intracerebroventricular (i.c.v.) administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical-CRF9-41 (alpha-HCRF) immediately before noise exposure. Intracerebroventricular injection of CRF (1 microgram) also decreased high-affinity choline uptake in the frontal cortex and the hippocampus of the rat, and these effects of CRF could be blocked by pretreating the animal with the narcotic antagonist naltrexone (1 mg/kg, i.p.). These results indicate that the effects of noise on central cholinergic systems are mediated by CRF and suggest a stressor-CRF-endogenous opioid-acetylcholine sequence of effects in the brain.     

Prenatal exposure to integerrimine N-oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood

Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6–20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood.     

The histopathological, behavioral and neurochemical effects of intraventricular injection of ethylcholine mustard aziridinium (AF64A) in the neonatal rat.

This study investigated the histopathological, behavioral and neurochemical effects of bilateral injection of 2.0, 0.5 and 0.1 nmol/ventricle ethylcholine aziridinium (AF64A) on postnatal day (PND) 2. The rats showed a significant, but non-dose-related reduction of choline acetyltransferase (ChAT) in the hippocampus but not the cerebral cortex or the caudate nucleus when sacrificed on PND 16. No effect on ChAT was found in any region at PND 58. The group given 2 nmol/ventricle were hyperactive and showed a deficit in spatial learning when tested on the Morris water maze at PND 38-43. No such differences were observed for the rats injected with 0.1 or 0.5 nmol/ventricle AF64A. This spatial learning impairment in the 2 nmol group was associated with non-specific tissue damage seen only in animals from this group that were sacrificed at PND 40. This tissue damage was most evident in the left medial frontal cortex, the caudate nuclei and the anterior dorsal hippocampus.     

Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats

Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.     

Prenatal experience and postnatal stress modulate the adult neurosteroid and catecholaminergic stress responses

Allopregnanolone (3α-hydroxy-5α-regnan-20-one) is a neuroactive steroid recently shown to be involved in the neurochemical stress response via its positive modulation of the GABA_A receptor complex. This experiment investigated the effects of postnatal stress (daily maternal separation during the first week of life) on the subsequent adult response to a stressor (10 min forced swim) in Long–Evans rats from one of three prenatal treatment groups (alcohol, pair-fed and control). Indices of stress response were allopregnanolone concentrations in plasma, cortex and hippocampus, and dopamine and norepinephrine concentrations in prefrontal cortex, nucleus accumbens and striatum. Females had higher levels of allopregnanolone than males in both plasma and brain. Prenatal alcohol exposure combined with early maternal separation stress resulted in an increase in the endogenous levels of allopregnanolone in the prefrontal cortex and hippocampus of adult offspring in response to a stressor compared to subjects without a prior history of postnatal stress ; this effect was greater in females. This increased allopregnanolone was also associated with decreased dopamine and norepinephrine levels in the prefrontal cortex. In the prenatal alcohol-exposed offspring, postnatal maternal separation blunted the increase in dopamine levels in the striatum seen in both control groups. Postnatal maternal separation increased norepinephrine levels in the nucleus accumbens regardless of prenatal experience, while in the prefrontal cortex only prenatal diet condition (pair-feeding and alcohol) resulted in lower norepinephrine levels. The results of this experiment suggest that experience, both pre- and postnatal, can have long-term consequences for the developing neurochemical responses to stressors.     

Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function in juvenile guinea pigs

The neurodevelopmental consequences of prenatal glucocorticoid exposure are not well-understood, particularly in species that give birth to neuroanatomically mature offspring. In the present study, we hypothesised that repeated prenatal glucocorticoid administration would alter hypothalamo-pituitary-adrenal (HPA) function in juvenile guinea pig offspring. Pregnant guinea pigs were injected with betamethasone (1 mg/kg) or vehicle on gestational days 40, 41, 50, 51, 60 and 61 (six doses). Prenatal glucocorticoid exposure abolished the pituitary-adrenal response to maternal separation in juvenile males, but had no effect in female offspring. Indeed, female offspring (vehicle and betamethasone) did not mount a significant HPA response to separation at 10 days of age. Although there were no effects of prenatal glucocorticoid exposure on hippocampal or hypothalamic corticosteroid receptor expression or corticotrophin-releasing factor (CRF) mRNA, there were significant effects in the pituitary and adrenal; again males were more affected than females. Prenatal glucocorticoid exposure increased pituitary pro-opiomelanocortin and CRF receptor mRNA, and markedly decreased adrenocortical CYP17 mRNA. In conclusion, repeated prenatal glucocorticoid exposure has profound influences on HPA function and regulation in the juvenile guinea pig, and this involves altered regulation at the level of the pituitary and adrenal cortex. Furthermore, juvenile males appear to be more vulnerable to the effects of prenatal glucocorticoid exposure than females.     

Altered metabolic activity in the cerebral cortex of rats exposed to ketamine

Uptake of the metabolic marker, [³H]2-deoxy-D-glucose(2DG) was compared in rats given subanesthetic (50–100 mg/kg, i.p.) or anesthetic (200 mg/kg, i.v.) doses of ketamine with that in normal, unanesthetized rats. All doses of ketamine caused a relative increase of 2DG labeling in limbic regions, including the hippocampus, dentate gyrus, and cingulate, piriform, and entorhinal cortices. Striking 2DG-dense zones were confined to the molecular layer in the hippocampus, dentate gyrus, and entorhinal cortex. Sub-anesthetic doses of ketamine produced a relative reduction of 2DG uptake in layers 1-1V of granular somalosensory cortex while sparing up take in layer Va; therefore, the peak of dense uptake shifted from layer IV to layer Va. In regions of the somatosensory cortex which display a dysgranular layer IV, vertical columns of relatively dense 2DG uptake extended through all cortical layers. Columns of 2I) G label also occurred outside of S1, in visual and auditory areas. In the primary visual cortex, this dose of ketamine decreased 2DG uptake relative to secondary visual cortex. Alteration of 2DG uptake in various cortical regions might be the consequence of a ketamine-induced activation of specific neuronal pathways with special neurochemical features. During subanesthetic ketamine administration, peak 2DG uptake shifts from cortical layer IV, which receives specific thalamocortical input to layer Va which receives projections via intrinsic cortical circuits. The ketamine-induced shift in the laminar focus of sensory cortical metabolism may reflect a functional disconnection from peripheral sensory input and/or enhanced internal (corticocortical) processing. These changes are more apparent during ketamine administration at doses too low to induce anesthesia and may, therefore, reflect the metabolic events that occur when ketamine and its analogues are taken as drugs of abuse.     

Behaviour and hippocampus-specific changes in spiny mouse neonates after treatment of the mother with the viral-mimetic Poly I:C at mid-pregnancy

Epidemiological studies have suggested a link between prenatal exposure to bacterial or viral infections and subsequent development of mental disorders such as schizophrenia and autism. Animal models to study the prenatal origin of such outcomes of pregnancy have largely used conventional rodents which are immature at birth compared to the human neonate, and doses of the infective agent (i.e., lipopolysaccharide, Poly I:C) have been large enough to cause sickness behaviour in the mother. In this study we have used the spiny mouse (Acomys cahirinus) whose offspring have completed organogenesis at birth, and a single subcutaneous injection of a low (0.5 mg/kg) dose of polyriboinosinic–polyribocytidilic acid (Poly I:C) at mid gestation (20 days, term is 39 days). The treatment had no effect on maternal, fetal or neonatal survival, or postnatal growth of the offspring. However, offspring showed significant impairments in non-spatial memory and learning tasks, and motor activity. Brain histology examined at 1 and 100 days of age revealed significant decreases in reelin, increased GFAP expression, and increased numbers of activated microglia, specifically in the hippocampus. This study provides evidence that a prenatal subclinical infection can have profound effects on brain development that are long-lasting.     

The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats

A number of studies reveal that prenatal stress (PS) may induce an increased vulnerability to depression in offspring. Some evidences indicate that extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) signal system may play an important role in the molecular mechanism of depression. In the present study, we examined the effects of prenatal restraint stress on depression-like behavior in one-month offspring Sprague-Dawley rats and expression of ERK2, CREB, B-cell lymphoma-2 (Bcl-2) mRNA in the hippocampus, prefrontal cortex and striatum to explore the potential role of ERK–CREB pathway in mediating the behavioral effects of PS exposure. Our findings demonstrated that PS increased immobility time in forced swimming test and decreased expression of ERK2, CREB, Bcl-2 mRNA in the hippocampus and prefrontal cortex of juvenile offspring rats except for CREB in hippocampus of male offspring. Changes induced by PS were partly prevented by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. These findings suggested that the ERK–CREB system might be related with the depression-like behavior in juvenile offspring rats subjected to PS, in which NMDA receptors might be involved.     

Effect of prenatal exposure to phencyclidine on the postnatal development of the cholinergic system in the rat

The purpose of this study was to examine the effect of prenatal exposure to phencyclidine (PCP) on the postnatal development of the cholinergic system in the neostriatum and the neocortex. Pregnant females were injected daily with PCP (0.5 mg/kg s.c.) from conception to parturition. On postnatal day 21 or 35, pups were injected with a challenge dose of PCP (0.5 mg/kg s.c.). The levels of acetylcholine and choline were measured, as well as the incorporation of deuterium-labelled choline into newly synthesized acetylcholine in the frontal cortex and neostriatum. The data demonstrate that even at 21 days, rat pups exposed to PCP in utero were more sensitive to a challenge dose of PCP than the saline controls. Thus, a tolerance to PCP, even after a prolonged prenatal exposure did not develop.     

Prenatal stress in the rat alters 5-HT1A receptor binding in the ventral hippocampus

Exposure of a pregnant woman to physical and/or psychological stress might affect her offspring by promoting the development of various learning, behavioral and/or mood disorders in later life. The 5-HT1A and 5-HT2A receptors are prominently implicated in the modulation of anxiety and mood-related behaviors. Using a semi-quantitative radiolabel immunocytochemical analysis (immunobinding), we studied the effect of prenatal stress on binding of these two receptor subtypes in the hippocampus of 4-week-old male and female Fischer 344 rats. Levels of 5-HT1A immunobinding in the ventral hippocampus, which is primarily implicated in emotional processing, were significantly decreased in male offspring after prenatal stress. A trend towards a decrease was observed in the ventral hippocampus of females. In contrast, 5-HT1A immunobinding within the dorsal hippocampus, which is mainly related to learning and memory, was not affected by prenatal stress in offspring of either gender. Likewise, no significant differences between control and prenatally stressed rats were observed for levels of 5-HT2A immunobinding in either part of the hippocampus or gender. The observed reduction in hippocampal 5-HT1A receptor binding in male offspring after prenatal stress may have important consequences for adult anxiety- and depressive-like behavior.     

Black American Maternal Prenatal Choline,Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness

Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline. Black American women had lower 16-week gestation plasma choline than Whites. Lower choline was not related to obesity, income, or metabolic genotypes. Pregnant women in rural Uganda have higher choline levels than Black American women. Black Americans’ lower choline was associated with higher hair cortisol, indicative of higher stress. Lower maternal choline was associated with offsprings’ lower gestational age at birth and with decreased auditory P50 inhibition, a marker of inhibitory neuron development. Behavioral development was assessed on the Infant Behavior Questionnaire-R-SF (IBQ-R) at 3 months. Lower Black American maternal gestational choline was associated with lower infant IBQ-R Orienting/Regulation, indicating decreased attention and relation to caregivers. Additional evidence for developmental effects of choline in Black Americans comes from a randomized clinical trial of gestational phosphatidylcholine supplementation versus placebo that included 15 Black Americans. Phosphatidylcholine increased gestational age at birth and newborn P50 inhibition and decreased Social Withdrawn and Attention problems at 40 months of age in Black Americans’ offspring compared to placebo. Inhibitory and behavioral deficits associated with lower prenatal choline in offspring of Black American women indicate potential developmental predispositions to later mental illnesses that might be ameliorated by prenatal choline or phosphatidylcholine supplementation.