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Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphan.

Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREB(Serine-133)), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy.

Animals↗

Prepubescent children show the adult relationship between dermatoglyphic asymmetry and performance on sexually dimorphic tasks.

The dermatoglyphic pattern of dermal ridges that constitutes the human fingerprint is complete by the 16th foetal week and its development is thought to be influenced by prenatal hormones. Finger ridge count (FRC) is asymmetrical with the majority having more ridges on the finger tips of the right hand (R >) while the minority have more on the left (L >). In adults, the R > condition has been associated with male-typical, and the L > condition with female-typical, performance on sexually dimorphic tasks. Here we report that 60 prepubescent children showed the same sex difference and the same relationship as adults between FRC and task performance: girls and L > children performed a female-favouring task better while boys and R > children performed a male-favouring task better. This finding indicates that these sex-related task performance differences are not dependent on the activational effects of adult gonadal steroids. The implications of these findings for prenatal influences on neuropsychological development are discussed.

Aging↗

Influence of prenatal cocaine exposure on early language development: longitudinal findings from four months to three years of age.

The influence of prenatal cocaine exposure on children's language functioning was evaluated longitudinally at six time points from 4 months to 3 years of age. The Miami Prenatal Cocaine Study prospectively enrolled 476 full-term African-American infants at birth, categorized as cocaine-exposed (n = 253) or non-cocaine-exposed (n = 223) by maternal self-report and bioassays (maternal/infant urine, meconium). The Bayley Scales of Infant Development, scored using the Kent Scoring Adaptation for language, was administered at 4, 8, 12, 18, and 24 months. The Clinical Evaluation of Language Fundamentals-Preschool was administered at 3 years. In longitudinal analyses using Generalized Estimating Equations, cocaine-exposed children had lower overall language skills than non-cocaine-exposed children (D = -0.151; 95% CI = -0.269, -0.033; p =.012). Longitudinal findings remained stable after evaluation of potential confounding influences including other prenatal substance exposures and sociodemographic factors. Preliminary evidence also indicated possible mediation through an intermediary effect involving cocaine-associated deficits in fetal growth.

Case-Control Studies↗

Influence of prenatal and continuous postnatal protein-deficient diets on the development of rats.

The influence of prenatal and continuous postnatal protein-restricted diet on the development of rats was investigated. Virgin female rats were maintained for 35 days on isocaloric diets containing 8 or 25% casein, and then mated. The animals were supplied their respective diets during gestation and nursing. It was observed that the offspring of mothers kept on the 8% casein diet had 50% less body weight, and 10-15% less brain weight than the corresponding controls. The peak of rapid brain growth for both groups of animals occurred at age 6 days. The rate of de novo biosynthesis of sterols, following the injection of (2-14C)-mevalonic acid into the midline thalamic area and the cerebellum, was also investigated. A significant shift of the age of peaking of 14C-incorporation into sterols in the cerebellum was noted. Our results indicate that although unlimited amounts of food were supplied to the mothers on the 8% casein diet, this could not offset the detrimental effect of the protein deficiency on the offspring.

Animals↗

Etiology of alcoholism: relevance of prenatal hormonal influences on the brain, anomalous dominance, and neurochemical and pharmacological brain asymmetry.

Because of possible prenatal hormonal influences on the brain, leading to anomalous dominance, pharmacological and neurochemical asymmetry, and consequent antisocial personality and phobic anxiety, the subject ingests ethanol for its tension-reducing properties via endorphinergic activation and the dopaminergic reward system. Due to presence of stress, and effects of anomalous dominance on ethanol metabolizing enzymes, ethanol-oxidizing systems are activated leading to high rates of ethanol elimination from the blood, and thus the decreased intensity of reaction to ethanol, leading to tolerance. Since stress can cause a decrease in the number of opiate receptors, a vicious cycle of ingesting more and more ethanol may be instituted.

Alcoholism↗

Maternal factors that influence inadequate prenatal care.

Fifty-seven pregnant women who received inadequate prenatal care identified the factors that influenced their decisions related to prenatal care. Data were collected in an institution that serves neighborhood clinics that offer free prenatal care and can be reached by public transportation. Women were interviewed either prenatally (n = 23) or postnatally (n = 34). The interview questions were drawn from the literature on the adequacy of prenatal care. The women identified 22 personal reasons and structural barriers for receiving inadequate prenatal care. The five most frequently cited reasons were small children at home, no medical assistance card, didn't know reason, sadness or ambivalence about the pregnancy, and just moved to the area. Despite demographic risk and facing the similar barriers, some women manage to receive sufficient care and others do not. Presently, government and other policy-making groups often believe that public insurance, Medicaid, or socialized medicine is the answer to our high infant mortality rate. However, in some geographic areas where financial barriers are not factors and where services are available that meet pregnant women's needs, some women still do not enter care early and remain in care. Data that expand knowledge on why women receive inadequate prenatal care will be useful in developing community outreach programs, preparing public service announcements, and designing prenatal services.

Adolescent↗

Sex differences in corpus callosum: influence of prenatal alcohol exposure and maternal undernutrition.

The functional significance of sex differences in the size of the corpus callosum was investigated using a prenatal alcohol exposure paradigm that influences the fetal hormonal milieu. Adult male and female Long-Evans rats were selected from one of 3 prenatal treatment histories: prenatal alcohol-exposed (35% ethanol-derived calories), nutritional control (0% ethanol-derived calories) or standard control (lab chow). Subjects were assessed for open field activity at 85 days of age. At 100 days of age, midline sagittal areas of the corpus callosum and the anterior commissure were determined for these subjects. Male control subjects had significantly larger callosal areas than female controls. Prenatal alcohol exposure significantly decreased the total callosal area, and abolished this sexual dimorphism. When the callosal measurements were analyzed using Denenberg's regions, differential effects of prenatal alcohol exposure, undernutrition and sex were dissociable by subarea. There were no significant sex differences or effects of prenatal alcohol exposure in the midline sagittal area of the anterior commissure. Callosal size was negatively correlated to open field activity, suggesting a possible role in normal exploratory behavior and to the overactivity observed after prenatal alcohol exposure.

Animals↗

[Effectiveness of adrenergic transmission and mechanisms of its regulation in rats exposed to prenatal effects of ethanol].

Prenatal influence of ethanol doesn't induce the changes of 3H-NA secretion intensity from rat cerebral cortex slices, but induces an increase of coefficient of variation of 3H-NA secretion intensity. The self-facilitation and stabilization of secretion are described during study of 3H-NA secretion intensity in the series of successive depolarization of control animals slices. Prenatal influence of ethanol induces self-facilitation but destabilize 3H-NA secretion. The results show that prenatal influence of ethanol breaks of autoreceptors function which are a cause of 3H-NA secretion destabilization. The break of the higher nervous activity is followed by the break of regulation mechanisms of adrenergic transmission effectiveness which is induced by prenatal influence of ethanol.

Animals↗

Gender differences in influence of prenatal photoperiods on postnatal pineal melatonin rhythms and serum prolactin and follicle-stimulating hormone in the Siberian hamster (Phodopus sungorus).

In Siberian hamsters, the rate of testicular maturation during juvenile life can be influenced by both the prenatal photoperiod and the day length experienced postnatally. In this report, potential postnatal photoperiodic mechanisms modified by prenatal photoperiod were investigated in this species. The study examined the effect of prenatal photoperiodic history on the postnatal pineal melatonin (MEL) rhythm and on postnatal secretion of FSH and PRL. In the first study, the pineal MEL content of hamsters, gestated in either 16 h of light and 8 h of darkness/day (16L) or 10L and raised postnatally in 14L, was monitored at various times of the day and night at 18 days of age. We found that prenatal photoperiod did influence the postnatal pineal MEL rhythm in 18-day-old males, but a similar effect was not evident in females. For males, the durations of the nocturnal elevation of pineal MEL were 8.5 and 7 h in 16L and 10L gestated hamsters, respectively. However, MEL rhythms were similar to each other in the corresponding groups of females (8.5- and 9-h durations of elevated pineal MEL in 16L and 10L prenatal photoperiod groups, respectively). In a subsequent study using the same photoperiod paradigm, FSH and PRL concentrations were examined in both genders at 3- to 10-day intervals between 18-62 days of age. The serum PRL (day 22) and FSH (days 18 and 22) concentrations in males were significantly affected by prenatal photoperiod. Specifically, circulating serum PRL (on day 22) and FSH (on days 18 and 22) concentrations were increased substantially in 10L gestated, compared to 16L gestated, males raised in 14L after birth. In contrast, serum FSH concentrations in female hamsters were not different between 16L and 10L gestated groups at these times. In another study using the same experimental design, the pattern of testicular development was explored in males. Hamsters that had experienced a 10L photoperiod prenatally and were raised in 14L exhibited rapid testicular growth from 27-52 days of age compared to hamsters that had experienced a 16L prenatal photoperiod and were reared in 14L. These results support the hypothesis that in juvenile male hamsters exposed to 14L postnatally, endogenous MEL production and serum FSH concentrations are influenced by photoperiodic information received during fetal life. In addition, these findings help to explain why males gestated in 10L and raised in 14L exhibit accelerated testicular development in the first 2 months of life compared to males gestated in 16L and transferred to 14L after birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.

Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.

Animals↗

Influence of prenatal hypoxia on brain development: effects on body weight, brain weight, DNA, protein, acetylcholinesterase, 3-quinuclidinyl benzilate binding, and in vivo incorporation of [14C]lysine into subcellular fractions.

The influence of prenatal hypoxia on subsequent brain development in the young rat was investigated by examining body and brain weight, cerebral cortex wet weight, protein and DNA concentrations, acetylcholinesterase (AChE) activity, 3-quinuclidinyl benzilate (QNB)-binding levels, the relative amounts of protein in various subcellular fractions, and the in vivo incorporation of [14C]lysine into the protein of homogenate and subcellular fractions. Exposure of pregnant females to a mild hypoxia (9.1% O2, 10 h per day for the 9--11 days preceding birth) resulted in a reduced body weight in the pups and days 1 and 5 after birth; total cortical DNA was reduced but brain weight and protein content were unaffected, leading to a higher protein/DNA ratio in prenatally hypoxic pups. By 10 days of age these differences between prenatally hypoxic and control animals were no longer apparent. There were no differences between prenatally hypoxic and control animals in AChE and QNB binding per milligram cortex protein. The relative amount of synaptic membrane protein from the cerebral cortex was reduced at day 1 in prenatally hypoxic animals and the synaptic membrane fraction showed a higher level of incorporation of [14C]lysine on days 1, 5, and 10. The developmental profile of [14C]lysine incorporation showed a peak on day 10 which was higher in prenatally hypoxic rats. By 46 days after birth little difference could be found between prenatally hypoxic and control animals.

Acetylcholinesterase↗

Prenatal melatonin influences developmental changes of tachykinins in response to estradiol benzoate.

The developmental changes of hypothalamic, pituitary, striatum and pineal gland tachykinin concentrations, as well as the response to estradiol-benzoate (EB) administration, were studied in offspring of control and melatonin (MEL) treated mother rats. Female rats were studied throughout different phases of the sexual development: infantile, prepubertal and pubertal periods, in the four following groups; control-offspring+vehicle; control-offspring+EB; MEL-offspring+vehicle; MEL-offspring+EB. Hypothalamic NKA in control-offspring+ vehicle was significantly increased only at 27 days of age and in control-offspring+EB at 27 days of age and during the infantile period. Hypothalamic SP levels increased similarly in control-offspring+EB during the infantile period but the EB influence was more pronounced with significantly increased concentrations at 32 days of age. Prenatal melatonin treatment produced major alterations in these patterns of postnatal development. In MEL-offspring+EB tachykinins concentrations in the hypothalamus during infantile and prepubertal periods did not increase, however at 37 days of age, they showed significantly higher values than in control-offspring+EB groups. The developmental pattern of pituitary NKA and SP concentrations in both; control-offspring+vehicle and control-offspring+EB groups, showed similar values from the infantile period to puberty, indicating that NKA and SP concentrations remained at similar levels independently of the sexual stage, only at 27 days of age in control-offspring+EB significantly increased values were found as compared to MEL-offspring+EB. Prenatal melatonin did not produce marked modifications, only significantly lower NKA and SP concentrations in MEL-offspring+EB group were observed at 25 days of age in comparison to control-offspring+EB group. Striatal NKA and SP concentrations showed a similar developmental pattern. In control-offspring, EB treatment produced NKA and SP decreased concentrations at the infantile period than in control-offspring+vehicle and significantly increased concentrations during the prepubertal period, then during the pubertal period NKA and SP concentrations decreased in control-group+EB. However, prenatal melatonin treatment reduced the levels of striatal NKA and SP during the prepubertal period after EB treatment and delayed until pubertal period the increase previously observed in control group during the prepubertal period. In MEL-offspring+vehicle group striatal concentrations of both tachykinins remained at low levels from infantile period until pubertal period. Prenatal melatonin and EB did not produce major alterations in SP pineal concentrations throughout sexual development. Plasma estradiol concentrations were significantly higher in the groups that received EB treatment than in those that received vehicle during prepubertal and juvenile periods in control-offspring+EB group and during the pubertal period in MEL-offspring+EB group. These data indicate that prenatal MEL treatment may influence NKA and SP developmental pattern from the infantile period until adulthood in the female rat.

Animals↗

Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol.

Early life environmental factors are able to influence prenatal development and may cause structural and functional effects on hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitter systems in the offspring. These effects seem to be species specific and may depend on the period of gestation when the factors are effective. Elevated maternal cortisol levels are assumed to play a crucial role as a programming factor during prenatal development. Thus, the present study was performed in order to examine the effects of increased maternal cortisol levels during mid- and late gestation on central and peripheral alterations of the HPA axis and brain neurotransmitter profiles in piglets. Endogenous cortisol release was induced by i.m. administration of ACTH to sows every second day either during mid- (day 49 until 75) or late gestation (day 85 until 107). Controls received injections of saline. ACTH treatment of sows during mid- and late gestation had no effects on the gestation length, the number of total born and the frequency of stillborn piglets. However, ACTH treatment during late gestation caused an increase of birth weight (P < 0.04) and affected the organ:body weight ratios (brain and adrenal) in the offspring. There was an impact of increased maternal cortisol on the HPA axis and on central neurotransmitter systems in the offspring. ACTH treatment during mid gestation caused a significant decrease of plasma corticosteroid-binding globulin (CBG; P < 0.03) and an increase of the noradrenergic activity in the locus coeruleus (LC) region (P < 0.02). Elevated maternal cortisol during late gestation also produced a significant decrease of plasma CBG (P < 0.05), but significantly increased the plasma noradrenaline (NA) concentration (P < 0.02) and decreased the serotonergic activity in the LC at both postnatal day 1 (P < 0.016) and day 28 (P < 0.003). Furthermore, there were sex-specific effects of ACTH treatment on plasma CBG, NA and brain monoamine turnover, with more pronounced changes in male offspring. In conclusion, elevated maternal cortisol levels during mid- and late gestation in pigs affect growth, HPA axis and brain neurotransmitter systems in the offspring in a sex-specific manner. The observed alterations in endocrine and neurotransmitter systems are dependent on the gestational period. Late gestation appears to be a more sensitive phase for cortisol-induced programming in pigs. Moreover, the present data show that there are marked developmental differences between laboratory animals and domestic pigs, and highlight the importance of species-specific studies on prenatal influences.

Adrenal Glands↗

Influence of prenatal and postnatal exposure to passive smoking on infants' health during the first six months of their life.

On the Czech set of European Longitudinal Study of Pregnancy and Childhood (ELSPAC), we tried to verify whether it is possible to confirm the results of foreign studies which found out that the both prenatal and postnatal exposure of newborns to chemicals on cigarette smoke could influence the newborns' morbidity in the first six months of their life. Mothers, who served as sources of data about their smoking behaviour during the pregnancy and after the birth as well as information about the health status of the children after the birth (N=3,871) were divided into four groups: 1. women who never smoked (74.3%), 2. women who stopped smoking in pregnancy and started to smoke after delivery (18.3%), 3. women who smoked both during pregnancy and after delivery (7.2%), 4. women who smoked during pregnancy and stopped after delivery. Unfortunatelly, the last group was very small (only seven mothers) and did not allow assessment of exclusively prenatal exposition. Sucklings from Czech ELSPAC set exposed to chemicals in cigarette smoke either only after the birth or also during the prenatal period, showed significantly higher occurence of different symptoms of respiratory tract damages and their complications (like otitis media) when compared to children of non smoking mothers. Due to illnesses during the first six months after the birth, their parents had to look more often for the consultations of physician, including hospitalization. Our results, as well as results of foreign studies, confirm, that smoking of mothers during the pregnancy and after the birth represents significant risk for the first months of life. Illnesses of children in this early period can cause longitudinal consequences which emerge during the childhood as well as in adulthood. They also represent a strong stressogenic factor. Children's health consequences of exposure to cigarette smoke request very often intensive and expensive care within health system. Our results are the same as those of foreign studies and confirm that both prenatal and postnatal exposure to chemicals of cigarette smoke is significant risk factor which negatively influences the health status on the early periods life.

Analysis of Variance↗

Influence of prenatal ethanol exposure on cholinergic development in the rat striatum.

This study investigated the influence of ethanol exposure throughout gestation on cholinergic development within the rat striatal region. Pregnant Long-Evans rats were maintained on three diets throughout gestation: A liquid diet in which ethanol accounted for 35-39% of the total calories, a similar diet with the isocaloric substitution of sucrose for ethanol, and a lab chow control diet. At postnatal days 14 and 60 (P14 and P60), the striatal regions of the offspring were analyzed for the number of cholinergic neurons, via choline acetyltransferase (ChAT) immunostaining. The area of the striatum was also measured in these animals. At P14, P21, and P60, ChAT activity was assessed in the same region. These analyses revealed a significant increase in the number of cholinergic striatal neurons at P14 in the animals which had been exposed prenatally to ethanol. This increase was transient, however, with equal numbers of ChAT-positive cells found in all three groups by adulthood (P60). The brain weights of the ethanol-exposed animals were significantly reduced at P14 and P21, but were comparable to controls by P60. There were no significant differences in the striatal area or the overall volume of the region assessed, however, at either P14 or P60. Although there were some increases in ChAT activity across the ages viewed (most notably between P14 and P21), there were no effects of diet on ChAT activity at any age assessed. It is proposed that the increased numbers of cholinergic neurons could be a function of errors in migration, enhanced neurogenesis, diminished cell death, alterations in gene expression, or increased cell survival as a result of alterations in neurotrophic factor production or availability.

Age Factors↗

Age at menarche: Influences of prenatal and postnatal growth.

OBJECTIVE: The objective of this study was to determine the influence of birth weight and postnatal weight gain on age at menarche. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study where girls from the West Australian Pregnancy (Raine) Cohort Study were followed prospectively from fetal life (18 wk of pregnancy) to adolescence (12-14 yr). MAIN OUTCOME MEASURE: Age at menarche was the main outcome measure. RESULTS: Growth status at birth was judged by expected birth weight ratio (EBW; a ratio of observed infant's birth weight over median birth weight appropriate for maternal age, weight, height, parity, infant sex, and gestational age). Postnatal growth status was judged by body mass index (BMI). Both EBW (P = 0.020) and BMI in childhood (8 yr of age) (P < 0.001) were associated with age at menarche. Menarche occurred earlier in girls with lower EBW and higher BMI. CONCLUSIONS: We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche. Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche. Lower EBW combined with higher BMI during childhood predicted early age at menarche, and this relationship existed across normal birth weight and BMI ranges.

Adolescent↗

The influence of prenatal exposure to different salt diets on body and organ weights in newborn Dahl rats.

Present study tried to evaluate the influence of different diets (low- and high-salt, bicarbonate) administered during prenatal period on body and organ weights of newborn Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Blood pressure of DR dams was not influenced by dietary loading but it was significantly increased by high-salt diet in DS rats. Blood pressure of all DS dams was higher when compared to the respective DR rats. There were significant negative correlations between mean arterial pressure of DS (but not DR) dams and body weight of newborns in all dietary groups. Litter sizes were comparable in all groups studied. High-salt diet increased body weight and relative heart weight of newborns of both genotypes. On the other hand, the influence of bicarbonate diet on body weight was more pronounced in DS pups whereas the effect on relative heart weight was seen only in DR newborns. The relative heart and kidney weights were significantly higher and relative liver weight significantly lower in newborns of DR dams when compared to those of DS dams irrespective of mother's diet. There was a tendency in all organs of DS newborns to contain less water in comparison with respective DR pups. It should be noted that in newborns of both genotypes bicarbonate diet lowered relative DNA content more than relative protein content. In conclusion, high-salt and bicarbonate diets exert dissimilar effects on prenatal body and organ development in Dahl rats.

Animals↗