Dataset Information

Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ?FosB.

ABSTRACT: Elucidating mechanisms by which physical exercise promotes resilience, the brain's ability to cope with prolonged stress exposure while maintaining normal psychological functioning, is a major research challenge given the high prevalence of stress-related mental disorders, including major depressive disorder. Chronic voluntary wheel running (VWR), a rodent model that mimics aspects of human physical exercise, induces the transcription factor ?FosB in the nucleus accumbens (NAc), a key reward-related brain area. ?FosB expression in NAc modulates stress susceptibility. Here, we explored whether VWR induction of NAc ?FosB promotes resilience to chronic social defeat stress (CSDS). Male young-adult C57BL/6J mice were single housed for up to 21 d with or without running wheels and then subjected to 10 d of CSDS. Stress-exposed sedentary mice developed a depressive-like state, characterized by anhedonia and social avoidance, whereas stress-exposed mice that had been wheel running showed resilience. Functional inhibition of NAc ?FosB during VWR, by viral-mediated overexpression of a transcriptionally inactive JunD mutant, reinstated susceptibility to CSDS. Within the NAc, VWR induction of ?FosB was CREB-dependent, associated with altered dendritic morphology, and medium spiny neuron (MSN) subtype specific in the NAc core and shell subregions. Finally, when mice performed VWR following the onset of CSDS-induced social avoidance, VWR normalized such behavior. These data indicate that VWR promoted resilience to CSDS, and suggest that sustained induction of ?FosB in the NAc underlies, at least in part, the stress resilience mediated by VWR. These findings provide a potential framework for the development of treatments for stress-associated mental illnesses based on physical exercise.

SUBMITTER: Mul JD

PROVIDER: S-EPMC6046059 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ΔFosB.

Mul Joram D JD Soto Marion M Cahill Michael E ME Ryan Rebecca E RE Takahashi Hirokazu H So Kawai K Zheng Jia J Croote Denise E DE Hirshman Michael F MF la Fleur Susanne E SE Nestler Eric J EJ Goodyear Laurie J LJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180524 9

Elucidating mechanisms by which physical exercise promotes resilience, the brain's ability to cope with prolonged stress exposure while maintaining normal psychological functioning, is a major research challenge given the high prevalence of stress-related mental disorders, including major depressive disorder. Chronic voluntary wheel running (VWR), a rodent model that mimics aspects of human physical exercise, induces the transcription factor ΔFosB in the nucleus accumbens (NAc), a key reward-rel ...[more]

PMID: 29875450

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Project description:Rats selectively bred for high (HCR) and low (LCR) aerobic capacity show a stark divergence in wheel running behavior, which may be associated with the dopamine (DA) system in the brain. HCR possess greater motivation for voluntary running along with greater brain DA activity compared to LCR. We recently demonstrated that HCR are not immune to ovariectomy (OVX)-associated reductions in spontaneous cage (i.e. locomotor) activity. Whether HCR and LCR rats differ in their OVX-mediated voluntary wheel running response is unknown.To determine whether HCR are protected from OVX-associated reduction in voluntary wheel running.Forty female HCR and LCR rats (age ~27weeks) had either SHM or OVX operations, and given access to a running wheel for 11weeks. Weekly wheel running distance was monitored throughout the intervention. Nucleus accumbens (NAc) was assessed for mRNA expression of DA receptors at sacrifice.Compared to LCR, HCR ran greater distance and had greater ratio of excitatory/inhibitory DA mRNA expression (both line main effects, P<0.05). Wheel running distance was significantly, positively correlated with the ratio of excitatory/inhibitory DA mRNA expression across animals. In both lines, OVX reduced wheel running (P<0.05). Unexpectedly, although HCR started with significantly greater voluntary wheel running, they had greater OVX-induced reduction in wheel running than LCR such that no differences were found 11weeks after OVX between HCROVX and LCROVX (interaction, P<0.05). This significant reduction in wheel running in HCR was associated with an OVX-mediated reduction in the ratio of excitatory/inhibitory DA mRNA expression.The DA system in the NAc region may play a significant role in motivation to run in female rats. Compared to LCR, HCR rats run significantly more, which associates with greater ratio of excitatory/inhibitory DA mRNA expression. However, despite greater inherent motivation to run and an associated brain DA mRNA expression profile, HCR rats are not protected against OVX-induced reduction in wheel running or OVX-mediated reduction in the ratio of excitatory/inhibitory DA receptor mRNA expression. OVX-mediated reduction in motivated physical activity may be partially explained by a reduced ratio of excitatory/inhibitory DA receptor mRNA expression for which intrinsic fitness does not confer protection.

Dataset Information

Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ?FosB.

Publications

Voluntary wheel running promotes resilience to chronic social defeat stress in mice: a role for nucleus accumbens ΔFosB.

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