Acute exercise enhances fear extinction through a mechanism involving central mTOR signaling.

Autor: Moya NA; Department of Psychology, University of Colorado Denver, USA; Department of Integrative Biology, University of Colorado Denver, USA., Tanner MK; Department of Psychology, University of Colorado Denver, USA; Department of Integrative Biology, University of Colorado Denver, USA., Smith AM; Department of Psychology, University of Colorado Denver, USA., Balolia A; Department of Psychology, University of Colorado Denver, USA; Department of Integrative Biology, University of Colorado Denver, USA., Davis JKP; Department of Psychology, University of Colorado Denver, USA., Bonar K; Department of Psychology, University of Colorado Denver, USA., Jaime J; Department of Psychology, University of Colorado Denver, USA., Hubert T; Department of Psychology, University of Colorado Denver, USA., Silva J; Department of Psychology, University of Colorado Denver, USA., Whitworth W; Department of Psychology, University of Colorado Denver, USA., Loetz EC; Department of Psychology, University of Colorado Denver, USA., Bland ST; Department of Psychology, University of Colorado Denver, USA., Greenwood BN; Department of Psychology, University of Colorado Denver, USA.
Jazyk: angličtina
Zdroj: Neurobiology of learning and memory [Neurobiol Learn Mem] 2020 Dec; Vol. 176, pp. 107328. Date of Electronic Publication: 2020 Oct 17.
DOI: 10.1016/j.nlm.2020.107328
Abstrakt: Impaired fear extinction, combined with the likelihood of fear relapse after exposure therapy, contributes to the persistence of many trauma-related disorders such as anxiety and post-traumatic stress disorder. Identifying mechanisms to aid fear extinction and reduce relapse could provide novel strategies for augmentation of exposure therapy. Exercise can enhance learning and memory and augment fear extinction of traumatic memories in humans and rodents. One factor that could contribute to enhanced fear extinction following exercise is the mammalian target of rapamycin (mTOR). mTOR is a translation regulator involved in synaptic plasticity and is sensitive to many exercise signals such as monoamines, growth factors, and cellular metabolism. Further, mTOR signaling is increased after chronic exercise in brain regions involved in learning and emotional behavior. Therefore, mTOR is a compelling potential facilitator of the memory-enhancing and overall beneficial effects of exercise on mental health.The goal of the current study is to test the hypothesis that mTOR signaling is necessary for the enhancement of fear extinction produced by acute, voluntary exercise. We observed that intracerebral-ventricular administration of the mTOR inhibitor rapamycin reduced immunoreactivity of phosphorylated S6, a downstream target of mTOR, in brain regions involved in fear extinction and eliminated the enhancement of fear extinction memory produced by acute exercise, without reducing voluntary exercise behavior or altering fear extinction in sedentary rats. These results suggest that mTOR signaling contributes to exercise-augmentation of fear extinction.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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