Long-term effects of neonatal maternal deprivation and ACTH on hippocampal mineralocorticoid and glucocorticoid receptors

Twenty-four hours of maternal deprivation result in activation of the infant rat’s adrenocortical axis. In the present study we examined the long-term effects of maternal deprivation on the corticosterone (Cort) response to stress. Pups were maternally deprived (Dep) on postnatal day( PND) 11 and tested immediately ( PND 12) or returned to their mothers and tested at later ages. Testing consisted of a time course of the Cort response to a saline injection (5, 15, 30, and 60 min). At PND 12, the response of Dep pups was higher than that of nondeprived (non-Dep) pups. No group differences were observed at PND 16 and 22. On PND 30, Dep rats showed lower Cort levels than non-Dep pups at 0, 5, and 30 min after saline. At PND 60, non-Dep females showed higher Cort levels than males at 5, 15, and 30 min. This gender difference for Dep pups was observed only at 5 min. Male and female Dep animals presented lower Cort levels than non-Dep counterparts at 60 and 30 min after saline, respectively. These findings indicate that maternal deprivation effects on Cort secretion are long lasting. Dep rats showed a smaller adrenal response to stress at PND 30, whereas as adults the stress response was similar but the turnoff was different.

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Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7390516 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Branka Marković ◽

Nevena V. Radonjić ◽

Gordana Jevtić ◽

Tihomir Stojković ◽

Milica Velimirović ◽

...

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Complex I ◽

Redox Regulation ◽

Maternal Deprivation ◽

Long Term Effects ◽

Caudate Nuclei ◽

Oxidative Stress Parameters ◽

Stress Parameters

Maternal deprivation (MD) causes perinatal stress, with subsequent behavioral changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of the major generators of reactive oxygen species, known to play a role in stress response in different tissues. The aim of this study was to elucidate the long-term effects of MD on the expression of NADPH oxidase subunits (gp91phox, p22phox, p67phox, p47phox, and p40phox). Activities of cytochrome C oxidase and respiratory chain Complex I, as well as the oxidative stress parameters using appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats were exposed to a 24 h maternal deprivation and sacrificed at young adult age. The structures affected by perinatal stress, cortex, hippocampus, thalamus, and caudate nuclei were investigated. The most prominent findings were increased expressions of gp91phox in the cortex and hippocampus, increased expression of p22phox and p40phox, and decreased expression of gp91phox, p22phox, and p47phox in the caudate nuclei. Complex I activity was increased in all structures except cortex. Content of reduced glutathione was decreased in all sections while region-specific changes of other oxidative stress parameters were found. Our results indicate the presence of long-term redox alterations in MD rats.

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Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

BioMed Research International ◽

10.1155/2014/235238 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Milan Aksić ◽

Nevena V. Radonjić ◽

Dubravka Aleksić ◽

Gordana Jevtić ◽

Branka Marković ◽

...

Keyword(s):

Animal Model ◽

Morphological Changes ◽

Maternal Deprivation ◽

Retrosplenial Cortex ◽

Control Group ◽

Long Term Effects ◽

Adult Rats ◽

Adult Age ◽

Neuronal Soma

Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition.

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Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

BioMed Research International ◽

10.1155/2014/636574 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Branka Marković ◽

Nevena V. Radonjić ◽

Milan Aksić ◽

Branislav Filipović ◽

Nataša Petronijević

Keyword(s):

Cholinergic System ◽

Ache Activity ◽

Maternal Separation ◽

Adult Life ◽

Brain Regions ◽

Maternal Deprivation ◽

Control Group ◽

Long Term Effects ◽

Activity Measurements

Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD) produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach) release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE) activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS) cortex. Wistar rats were separated from their mothers on the postnatal day (P) 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

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Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats

Developmental Neuroscience ◽

10.1159/000512223 ◽

2020 ◽

Vol 42 (2-4) ◽

pp. 145-158

Author(s):

Oleg Vetrovoy ◽

Ekaterina Tyulkova ◽

Viktor Stratilov ◽

Kseniia Baranova ◽

Peter Nimiritsky ◽

...

Keyword(s):

Stress Response ◽

Glucocorticoid Receptors ◽

Hippocampal Formation ◽

Prenatal Hypoxia ◽

Male Rats ◽

Blood Levels ◽

Hepatic Glycogen ◽

Negative Consequences ◽

Long Term Effects

Introduction: Prenatal hypoxia is a risk factor for the development of numerous neurological disorders. It is known that the maternal stress response to hypoxia determines the epigenetic impairment of the perinatal expression of glucocorticoid receptors (GR) in the hippocampus of the progeny, but so far no detailed study of how this affects the functional state of the glucocorticoid system during further ontogenesis has been performed. Objective: The goal of the present study was to examine the long-term effects of the prenatal hypoxia on the functioning of the glucocorticoid system throughout life. Methods: Prenatal severe hypobaric hypoxia (PSH) was induced in the critical period of embryonic hippocampal formation on days 14–16 of gestation in a hypobaric chamber (180 Torr, 5% oxygen, 3 h). The activity of central (hippocampus) and peripheral (liver) components of the glucocorticoid system was assessed in 1-day-old (newborn), 2-week-old (juvenile), 3-month-old (adult), and 18-month-old (aged) male rats. Results: The PSH resulted in continuously elevated baseline corticosterone blood levels in the adult and aged rats. The chronic elevation of the corticosterone levels was accompanied by a progressive deficit of the GR expression in the liver, increased hepatic glycogen content, dysregulated glucose-6-phosphatase activity, and eventually hypoglycemia. Elevated corticosterone appears to result from the impairment of the mechanisms of glucocorticoid negative feedback since a substantial decrease in both the total number of GR and their nuclear localization was observed already in the hippocampus of newborn rat pups and persisted throughout life. Corresponding stable hippocampal downregulation of GR-dependent genes was observed as well. Suppression of the maternal glucocorticoid stress response to hypoxia by metyrapone injection to pregnant rats prior to each hypoxic challenge considerably reduced corticosterone over-response to hypoxia and prevented reduced hippocampal GR. Conclusions: Our findings demonstrate that in progeny a deficit of hippocampal GR resulting from maternal glucocorticoid response to hypoxia remains stable throughout life and is accompanied by severe disturbances of baseline glucocorticoid levels and its peripheral reception. Negative consequences of PSH can be prevented by injection with an inhibitor of corticosterone synthesis (metyrapone) to pregnant females undergoing hypoxia.

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