Corrigendum to “The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation” [Dev. Brain Res. 139 (2002) 39–49

The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation

These studies investigated behavioral and hormonal responses to stress in developing mice. Experiment 1 examined the effects of 24-hr maternal deprivation on corticosterone (CORT) secretion and ultrasonic vocalization (UVZ) rate in 4-, 8-, and 12-day-old mice. At these ages, exposure to a novel environment resulted in minimal changes in CORT secretion. Maternal deprivation increased pups' CORT secretion in an age-dependent fashion but did not affect their UVZ rate. The aim of experiment 2 was to test the effects of chlordiazepoxide (CDP), an anxiolytic compound, on CORT secretion and UVZ in both normally reared and in maternally deprived 8-day-old mice. CDP administration elevated CORT secretion in a dose-dependent fashion, producing larger CORT increases in deprived (DEP) animals. CDP affected UVZ only in nondeprived (NDEP) animals: UVZ rate was decreased by high CDP doses. Overall, these findings demonstrate that the infant mouse shows a period of stress hyporesponsiveness similar to the rat and that maternal presence contributes to inhibit adrenocortical activity. CDP administration, but not novelty exposure, increased CORT secretion in 8-day-old normally reared mice suggesting that during the stress hyporesponsive period, the HPA axis is capable of responding only to specific stimuli. Changes in HPA axis activity and UVZ rate resulting from maternal deprivation and/or CDP challenge do not seem to be directly related.

Objective To investigate the effects of maternal deprivation on chronic stress-induced depression behavior and its characteristics in adult rats, and to evaluate the effects of maternal deprivation on the efficacy of escitalopram. Methods Newborn SD male rats were randomly divided into control(C) group, maternal deprivation (MD) group, chronic unpredictable stress (CUPS) group, maternal deprivation and chronic unpredictable stress (MD+ CUPS) group. Rats in control group received no experimental handling.Rats in MD group and MD+ CUPS group received maternal deprivation from the lst day after birth for 14 days.Rats in CUPS group and MD+ CUPS group received chronic unpredictable stress from 10 th weeks after birth for 28 days. Screened the rats with depression behaviors and treated them with escitalopram for 4 weeks. Results The incidence of anhedonia was significantly different among 4 groups (χ2=143.24, P CUPS group (40.98%) > MD group (17.11%) >C group (4.17%), P<0.0083). The incidence of behavioral despair was significantly different among 4 groups (χ2=70.34, P<0.05). Pairwise comparison showed the incidence of behavioral despair in MD+ CUPS group (43.43%) and CUPS group (39.34%) were significantly higher than that in MD group (13.51%) and C group (3.33%), but no difference was observed between MD+ CUPS and CUPS group (P<0.0083). The incidence of behavioral despair in MD group was significant higher than that in C group. There was no significant efficacy of escitalopram on anhedonia and behavioral despair among 3 stressed models. However the recovery incidence from anhedonia (44/140) was significantly lower than that from behavioral despair (76/140) (χ2=14.93, P<0.05). Conclusion The maternal deprivation increases the stress sensitivity and the incidences of anhedonia in adult rats.The efficacy of escitalopram on behavioral despair is higher than that on anhedonia without influence from maternal deprivation. Key words: Maternal deprivation; Chronic unpredictable stress; Anhedonia; Behavioral despair; Escitalopram

Effects of maternal deprivation and environmental enrichment on anxiety-like and depression-like behaviors correlate with oxytocin system and CRH level in the medial-lateral habenula

Early life experiences such as maternal deprivation (MD) exert long-lasting changes in adult behaviour and reactivity to stressors. Adolescent exposure to cannabinoids is a predisposing factor in developing certain psychiatric disorders. Therefore, the combination of the two factors could exacerbate the negative consequences of each factor when evaluated at adulthood. The objective of this study was to investigate the long-term effects of early MD [24 hours at postnatal day (PND) 9] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (0.4 mg/kg, PND 28-42) on diverse behavioural and physiological responses of adult male and female Wistar rats. We tested them in the prepulse inhibition (PPI) of the startle response and analysed their exploratory activity (holeboard) and anxiety (elevated plus maze, EPM). In addition, we evaluated their adrenocortical reactivity in response to stress and plasma leptin levels. Maternal behaviour was measured before and after deprivation. MD induced a transient increase of maternal behaviour on reuniting. In adulthood, maternally deprived males showed anxiolytic-like behaviour (or increased risk-taking behaviour) in the EPM. Adolescent exposure to the cannabinoid agonist induced an impairment of the PPI in females and increased adrenocortical responsiveness to the PPI test in males. Both, MD and adolescent cannabinoid exposure also induced sex-dependent changes in plasma leptin levels and body weights. The present results indicate that early MD and adolescent cannabinoid exposure exerted distinct sex-dependent long-term behavioural and physiological modifications that could predispose to the development of certain neuropsychiatric disorders, though no synergistic effects were found.

Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: Effect of maternal deprivation

Event Abstract Back to Event The effects of maternal deprivation on behavioural, neurochemical and neurobiological indices related to dopaminergic activity Georgia Rentesi1*, Katerina Antoniou1, Marios Marselos1 and Maria Konstandi1 1 University of Ioannina, Department of Pharmacology, School of Medicine, Greece Early maternal deprivation(MD)has been considered as an animal model of neurodevelopmental stress,which has been associated with abnormalities during adulthood that resemble specific symptoms of schizophrenia.The present study investigated specific behavioral,neurochemical and neurobiological parameters related to dopaminergic function in MD and control rats.Behavioral responses,such as the spontaneous activity in the open field,the response to d-amphetamine(d-amp)and the susceptibility to apomorphine, were evaluated in MD rats in adulthood.Dopamine(DA)levels,its metabolites along with turnover ratios of DA(DOPAC/DA and HVA/DA)and the DA biosynthesis ratios DA/DOPAC and DA/HVA)were assessed in the striatum,nucleus accumbens,prefrontal cortex and amygdala.The protein expression of D2 receptors in the respective brain regions was also assessed.Compared to controls,MD rats had increased spontaneous motor activity and an exaggerated motor activity following d-amp administration.Apomorphine-induced gnawing in MD rats was markedly increased compared to control rats.Neurochemical findings indicated increased dopaminergic activity as deduced by enhanced DA turnover ratios (DOPAC/DA or HVA/DA) in the striatum,amygdala and prefrontal cortex of MD as compared to control rats.Interestingly,increased DA biosynthesis ratio (DA/DOPAC and DA/HVA) was observed in the nucleus accumbens of MD rats.D2 receptor protein levels were increased in striatum, while they were lower in prefrontal cortex of MD rats compared to controls.Our data show that early MD stress may produce long term modifications in various behavioural, neurochemical and neurobiological indices. These indices demonstrate that MD stress produced persistent alterations in dopaminergic systems of specific brain regions that have been suggested to be implicated in the pathophysiology of schizophrenia.This research project is co-financed by E.U.-European Social Fund(75%)and the Greek Ministry of Development-GSRT(25%). Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Rentesi G, Antoniou K, Marselos M and Konstandi M (2009). The effects of maternal deprivation on behavioural, neurochemical and neurobiological indices related to dopaminergic activity. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.275 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2009; Published Online: 12 Jun 2009. * Correspondence: Georgia Rentesi, University of Ioannina, Department of Pharmacology, School of Medicine, Ioannina, Greece, grentesi@cc.uoi.gr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Georgia Rentesi Katerina Antoniou Marios Marselos Maria Konstandi Google Georgia Rentesi Katerina Antoniou Marios Marselos Maria Konstandi Google Scholar Georgia Rentesi Katerina Antoniou Marios Marselos Maria Konstandi PubMed Georgia Rentesi Katerina Antoniou Marios Marselos Maria Konstandi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Objective To observe the effect of maternal deprivation(MD) on learning and memory ability and hippocampal pathology and nestin expression in rats with hypoxic-ischemic brain damage (HIBD). Methods The models of HIBD SD male rats were established by the method of Rice, and were randomly divided into 2 groups: MD group and control group.In addition, the sham-operation group(sham group) models were established.The MD group rats were separated from their mother 3 hours per day from the second day after modeling to the 21st postnatal day.After 28 postnatal days, Morris water maze was used to evaluate the learning and memory ability of the rat models.HE staining was employed to observe the hippocampal pathological change in the rats.Then, the expression of nestin in the hippocampus was measured by the method of immunohistochemistry. Results Their body mass changes showed that quality of sham group was higher than that of the control and the MD groups, and quality was improved in the control group, compared with the MD group, and the differences were statistically significant(q=9.860 8, 3.880 7, 5.980 1, all P<0.05). The water maze scores of the MD group in place navigation test and spatial probe test were much lower than that of the control group and the sham group, and the scores of the sham group were higher than that of the control group, the differences were statistically significant(all P<0.05). The findings of HE stain showed that the pathology in the right-sided hippocampus of the sham group was normal and neurons were well-arranged, and that of control group was minimally abnormal, and the neurons were almost arranged orderly and remained normal.While, the pathomorphology of the MD group was obviously abnormal, the neurons were arranged disorderly, many of the neurons lost.According to the immunohistochemical findings, the number of nestin-positive cells in right-sided hippocampus of the MD group was significantly less than that of the control group, and the number of nestin-positive cells of the sham group was less than that of the MD group, which showed significant differences among the groups(all P<0.05). Conclusions MD aggravated injury to learning and memory ability of neonatal rats with HIBD, and decrease the number of nestin-positive cells of MD markedly, which is not good for the recovery of brain injury. Key words: Hypoxic-ischemic; Maternal deprivation; Learning and memory; Pathology; Nestin

Objective To investigate the effect of maternal deprivation (MD) on neurobehavior and PP1Cγgene expression in hippocampus. Methods Male pups were randomly divided into MD group(thirty-five)and control group(twenty-four). From PND 1 to PND 21 ,pups in the MD groups underwent daily maternal deprivation for 3 h ( Postnatal day). Neurobehavior was observed to investigate neurodevelopment, Morris water maze was used to measure spatial learning and memory,and Real-Time quantitative PCR was employed to analyze PP1Cγ gene expression. Results Several significant deficiencies were observed in bodyweight and grasping reflex while a great enhancement in hot-plate test in rat pups suffering from MD( (26.23 ± 2.81 )g vs. (30. 38 ± 3.85 )g;( 19.37 ± 11.89) s vs. (22.39 ± 17.62 ) s; (4.36 ± 1.76 ) s vs. ( 5.26 ± 2.55 ) s; P ＜ 0. 05 ), but deficiencies in neurological reflexes were subtle ( ( 0.83 ±- 0.30 ) s vs. ( 0. 83 ± 0. 34 ) s; ( 3.68 ± 1.63 ) s vs. ( 5.61 ± 3. 01 ) s;( 3.00 ± 0.00 ) vs. ( 3.00 ± 0. 00); P ＞ 0. 05 ). MD had a subtle influence on spatial learning and memory (P ＞0.05). Meanwhile,MD could lead to PP1Cγ expression down-regulation on PND 22 ( (2.19 ±0.62) vs. (3.52 ±0.86), P＜0. 05)which was in line with early neurobehavior results. No difference was found compared with MD group and control group on PND60 ( ( 1.73 ± 0. 78 ) vs. ( 1.33 ± 0. 34); P ＞ 0.05 ). However, there was the up-regulation of PP1Cγexpression on PND 90 ( (2.85 ± 0. 34) vs. ( 1.34 ± 0.93 ); P ＜ 0.05 ). Conclusion MD alters early neurobehavior and hippocampal PP1Cγgene expression in the Wistar rats,but has a subtle effect on learning and memory. At the same time,MD can make PP1Cγexpression in the hippocampus varying with the age. Key words: Maternal deprivation; Hippocampus; Neurobehavior; PP1Cγ

In this study, the hypothesis was tested that infants deprived from maternal care show persistent changes in hypothalamic-pituitary-adrenal activity. For this purpose, we studied the effect of maternal deprivation in one cohort of the healthy ageing Brown Norway rat strain showing still more than 80% survival rate at 32 months of age. Three-day-old male Brown Norway rats were either maternally deprived for 24 h or remained with the dam. In 3, 12 and 30-32 months (young, adult, senescent) deprived rats and their nondeprived littermates (controls), we determined basal resting and stress-induced plasma adrenocorticotropic hormone (ACTH) and corticosterone as well as corticotropin releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus. Mineralocorticoid (MR) and glucocorticoid receptors (GR) in hippocampus and PVN were also assessed using in vitro cytosol binding and in situ hybridization. The effect of ageing per se showed that in the control nondeprived Brown Norway rats, basal corticosterone and ACTH concentrations did not change during life. However, with age, the corticosterone response to novelty stress became progressively attenuated, but prolonged, while there was an age-related increase in the ACTH response. CRH mRNA expression in PVN decreased with age. Hippocampal MR binding and MR mRNA expression in the dentate gyrus were reduced at senescence, as were the GR binding capacities in hippocampus and hypothalamus. Maternal deprivation did not affect survival rate, body weight, nor adrenal weight of the ageing Brown Norway rats. Basal corticosterone and ACTH levels were not affected by deprivation, except for a rise in basal corticosterone concentrations at 3 months. At this age, the corticosterone output in response to novelty was attenuated in the deprived rats. In contrast, a striking surge in novelty stress-induced corticosterone output occurred at midlife while, at senescence, the corticosterone and ACTH responses were attenuated again in the deprived animals, particularly after the more severe restraint stressor. CRH mRNA expression was reduced only during adulthood in the deprived animals. After maternal deprivation, the MR mRNA in dentate gyrus showed a transient midlife rise. GR binding in hypothalamus and hippocampus GR binding was reduced in young rats while, in the senescent deprived animals, a reduced GRmRNA expression was observed in PVN and hippocampal CA1. In conclusion, in the Brown Norway rat, ageing causes a progressive decline in corticosterone output after stress, which is paralleled at senescence by decreased MR and GR mRNA expression in hippocampus and hypothalamus. The long-term effects of maternal deprivation become manifest differently at different ages and depend on test conditions. The deprivation effect culminates in a midlife corticosterone surge and results at senescence in a strongly reduced corticosterone output.

The effects of maternal deprivation on the somatotrophic axis and neuropeptide Y (NPY) neuronal system in the hypothalamus of female lambs were evaluated. Twelve-week-old lambs were divided into two groups: the control (lambs stayed with mothers) and maternally deprived (MD; lambs separated for 3 days from mothers). The expression of immunoreactive (ir) somatostatin in the neurons of the periventricular nucleus (PEV) and in nerve terminals of the median eminence (ME), growth hormone (GH) in the adenohypophyseal cells and NPY in the neurons of the PEV and arcuate (ARC) nuclei of the hypothalamus using immunohistochemistry followed by the image analysis were estimated. Concentrations of GH in the blood plasma were determined by radioimmunoassay. The expression of ir somatostatin in the PEV and ME, ir NPY in the ARC and PEV, ir GH in adenohypophyseal cells, and blood plasma GH concentrations were greater (p<0.05) in MD than in the control lambs. In conclusion, MD affects the somatotrophic axis by enhancement of GH secretion via restraining of somatostatin output. The simultaneous increase of expression of hypothalamic ir NPY suggests NPY involvement in the regulation of psychoemotional stress through the somatotrophic axis in the female lambs.

Effect of Maternal Deprivation on N-Acetyltransferase Activity Rhythm in Blinded Rat Pups

Pregnant female C57BL/10JHir mice were irradiated whole-body at 9 days of gestation with a single acute dose of carbon-ion radiation. The average linear energy transfer (LET) of the carbon ions was 50 keV/microm within a spread-out Bragg peak (SOBP). The effects were studied by scoring changes in the postnatal development of the mice as well as in the pigmentation of the cutaneous coats and tail tips of their offspring 22 days after birth. The percentage of live births was reduced in mice exposed to carbon ions at doses greater than 0.5 Gy. The survival to day 22 was also reduced in mice exposed to carbon ions at doses greater than 0.75 Gy. Moreover, the body weight at day 22 was reduced in mice exposed to carbon ions at doses greater than 0.1 Gy. A comparison of the survival to day 22 after exposure to carbon ions with our previous results for 60Co gamma rays indicated that carbon ions were twice as effective as gamma rays. White spots were found in the mid-ventrum as well as in the tail tips of offspring exposed to carbon ions in utero. The frequency and the size of the white spots in the mid-ventrum and in the tail tips increased as the dose increased. Carbon ions appear to be slightly more effective than the gamma rays used in our previous study. In the ventral white spots, no melanocytes were observed in the epidermis, dermis and hair follicles. These results indicate that prenatal exposure to carbon ions has a greater effect on the postnatal development and survival of mice than does exposure to gamma rays, and that the relative biological effectiveness is greater than that for effects on melanocyte development.

Regulation of the developing hypothalamic–pituitary–adrenal axis in corticotropin releasing hormone receptor 1-deficient mice

Background: Early life stress (ELS) models such as maternal deprivation (MD) are used to in¬vestigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. Materials and Methods: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results. Results: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P&lt;0.05). However, MD significantly increased depression in both male and female rats (P&lt;0.05). Final¬ly, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P&lt;0.05). Conclusion: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, ex¬posure to novel objects decreases depression, while anxiety and empathy do not change signifi¬cantly with exposure to novel objects. [GMJ.2019;8:e1093]