Investigations of HPA function and the enduring consequences of stressors in adolescence in animal models

McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, C. R.; Waters, Patti

doi:10.1016/j.bandc.2009.06.003

Cited by 239 publications

(173 citation statements)

References 143 publications

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“…Our results are in line with studies that have shown that in stressed rats, significant increment in methylation of BDNF gene was associated with reduced BDNF expression [47]. BDNF and TrkB in the HPC can regulate HPA axis and related to stress responses [48]. Previous studies have shown that hippocampal damage, altered behavior, and BDNF expression are also found in stressed and aging rats [17,18].…”

Section: Discussionsupporting

confidence: 91%

Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

et al. 2015

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Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development.

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Section: Discussionsupporting

confidence: 91%

Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

et al. 2015

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“…However, since we did not observe any age effects in the light/dark EMT and on other behavioural variables in the EPM such as frequency and percentage of open arm entries and head dips, this difference in open arm time appears not be related primarily to an altered anxiety state in pubertal rats. It is well known that the stress responsiveness is increased during adolescent development (McCormick et al 2010 ;Romeo, 2010), therefore, it might be possible that the vehicle injection per se acted as a stronger stressor in pubertal rats, which might also contribute to the slightly more pronounced WIN effects in pubertal than adult rats.…”

Section: Emotional Behaviourmentioning

confidence: 99%

Cannabinoid exposure in pubertal rats increases spontaneous ethanol consumption and NMDA receptor associated protein levels

Klugmann

Klippenstein

Leweke

et al. 2011

Int. J. Neuropsychopharm.

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Recent evidence suggests an involvement of the endocannabinoid system in the regulation of emotional behaviour and ethanol intake. Here we investigated age-specific acute behavioural effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN) on anxiety-related behaviour and voluntary ethanol consumption in rats. Animals were treated with WIN (1.2 mg/kg)/vehicle at puberty onset on postnatal day (PD) 40, or at adulthood (PD 100). Animals were tested in the elevated plus-maze (EPM) and the light/dark emergence test (EMT) and for the initial response to alcohol in a free-choice ethanol consumption paradigm. Acute WIN treatment increased anxiety-related behaviours, and this effect was found to be partially more pronounced in pubertal than adult rats. Additionally, increased intake of higher ethanol solutions after cannabinoid treatment was only observed in pubertal rats. These drug-induced behavioural changes during puberty are paralleled by induction of the NR1 subunit of the NMDA receptor in the medial prefrontal cortex and the striatum. Moreover, pubertal but not adult WIN administration increased the levels of the scaffold protein Homer in these brain regions. Enhanced CB₁ receptor levels in the reinforcement system were also observed in pubertal compared to adult rats. These data support the notion that puberty is a highly vulnerable period for the aversive effects of cannabinoid exposure. In particular, augmented ethanol intake in pubertal cannabinoid-exposed animals might be related to some extent to increased emotional behaviour and in particular to enhanced NMDA and CB₁ receptor signalling.

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“…The role of glucocorticoid hormones (commonly referred to as stress hormones) in mediating the influence of the environment on the functional and structural plasticity of the hippocampus has been investigated extensively. Nonetheless, investigations of the role of stressors and stress hormones in shaping hippocampal structure and function during adolescence in animal models have been relatively few until recent years [reviewed in McCormick et al (2010a)]. There is, however, much reason to suspect that the effects of stressors and stress hormones would have different consequences in adolescence (generally considered between postnatal days 28 and 59 in rats) than in adulthood (more than postnatal day 59).…”

Section: Introductionmentioning

confidence: 99%

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood

McCormick¹,

Thomas²,

Sheridan³

et al. 2011

Hippocampus

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127

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The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

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Investigations of HPA function and the enduring consequences of stressors in adolescence in animal models

Cited by 239 publications

References 143 publications

Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats

Cannabinoid exposure in pubertal rats increases spontaneous ethanol consumption and NMDA receptor associated protein levels

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood

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