Journal ArticleDOI
Changes in the Prefrontal Glutamatergic and Parvalbumin Systems of Mice Exposed to Unpredictable Chronic Stress
Ryan Shepard,Laurence Coutellier +1 more
TLDR
It is hypothesized that chronic stress-induced enhancement of glutamatergic transmission in the PFC is a crucial contributing factor to changes within the prefrontal GABAergic and, specifically, PV system, and is associated with sex-specific changes in the mRNA expression of the NR2B subunit of the NMDA receptor.Abstract:
The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known risk factor of mood disorders including anxiety and depression. Abnormalities in PFC functioning have been well described in humans displaying stress-induced depressive symptoms, and hypoactivity of the PFC is now recognized to be a key feature of the depressed brain. However, little is known about the causes and mechanisms leading to this altered prefrontal functional activity in the context of stress-related mood disorders. We previously showed that unpredictable chronic mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV), an activity-dependent calcium-binding albumin protein expressed in a specific subtype of GABAergic neurons, highlighting a potential mechanism through which chronic stress leads to hypofunction of the PFC. In this study, we aimed to investigate the mechanisms by which chronic stress alters the prefrontal GABA system. We hypothesized that chronic stress-induced enhancement of glutamatergic transmission in the PFC is a crucial contributing factor to changes within the prefrontal GABAergic and, specifically, PV system. BALB/c male and female mice were exposed to daily handling (control) or 2 or 4 weeks of UCMS. Female mice displayed a more severe altered phenotype than males, as shown by increased anxiety- and depressive-like behaviors and deficits in PFC-dependent cognitive abilities, particularly after exposure to 2 weeks of UCMS. This behavioral phenotype was paralleled by a large increase in prefrontal PV messenger RNA (mRNA) and number of PV-expressing neurons, supporting our previous findings. We further showed that the expression of pre- and postsynaptic markers of glutamatergic transmission (VGlut1 presynaptic terminals and pERK1/2, respectively) onto PV neurons was increased by 2 weeks of UCMS in a sex-specific manner; this was associated with sex-specific changes in the mRNA expression of the NR2B subunit of the NMDA receptor. These findings provide evidence of increased glutamatergic transmission onto prefrontal PV neurons, particularly in female mice, which could potentially contribute to their increased PV expression and the extent of their behavioral impairment following UCMS. Finally, our analysis of activity of subcortical regions sending glutamatergic afferents to the PFC reveals that glutamatergic neurons from the basolateral amygdala might be specifically involved in UCMS-induced changes in prefrontal glutamatergic transmission.read more
Citations
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Journal ArticleDOI
The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice
Wen-Juan Zhang,Wen-Yu Cao,Yan-Qing Huang,Yan-Hui Cui,Bo-Xuan Tu,Lai-Fa Wang,Guang-Jing Zou,Yu Liu,Zhao-Lan Hu,Rong Hu,Chang-Qi Li,Xiao-Wei Xing,Fang Li +12 more
TL;DR: The results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.
Journal ArticleDOI
The structural reorganization of the prefrontal cortex during adolescence as a framework for vulnerability to the environment
TL;DR: The evidence for neuroanatomical changes during adolescence in the PFC, an important neural region involved in decision making and reward processing, is examined, arguing that the brain is most influenced by experience when developmental processes are occurring.
Journal ArticleDOI
Chemogenetic Inhibition of Infralimbic Prefrontal Cortex GABAergic Parvalbumin Interneurons Attenuates the Impact of Chronic Stress in Male Mice.
Nawshaba Nawreen,Nawshaba Nawreen,Evelin M. Cotella,Evelin M. Cotella,Rachel Morano,Parinaz Mahbod,Khushali S. Dalal,Maureen Fitzgerald,Susan E. Martelle,Benjamin A. Packard,Benjamin A. Packard,Ana Franco-Villanueva,Rachel D. Moloney,Rachel D. Moloney,James P. Herman,James P. Herman +15 more
TL;DR: A chemogenetic approach to inhibit IL PFC PV INs during stress indicates a role for PV Ins in driving chronic stress adaptation and support literature evidence suggesting cortical GABAergic INs as a therapeutic target in stress-related illnesses.
Journal ArticleDOI
Prior stress followed by a novel stress challenge results in sex-specific deficits in behavioral flexibility and changes in gene expression in rat medial prefrontal cortex.
TL;DR: Investigating attentional set-shifting in male and female rats following chronic restraint stress, a post-chronic stress rest period, and an acute novel stress challenge suggests chronic stress leads to sex-specific stress adaptation mechanisms that may contribute to sex differences in response to subsequent stress exposure.
Journal ArticleDOI
Long term effects of peripubertal stress on excitatory and inhibitory circuits in the prefrontal cortex of male and female mice.
Clara Bueno-Fernandez,Marta Perez-Rando,Julia Alcaide,Simona Coviello,Carmen Sandi,Esther Castillo-Gómez,Juan Nacher +6 more
TL;DR: In this article, a chronic peripubertal stress (PPS) protocol based on psychogenic stressors was applied to male and diestrus females to analyze the long-term effects of PPS on the excitatory and inhibitory circuitry of the adult prefrontal cortex (PFC), and whether these effects are sex-dependent.
References
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