2. Academic Validation
  3. Rapamycin exerts an antidepressant effect and enhances myelination in the prefrontal cortex of chronic restraint stress mice

Rapamycin exerts an antidepressant effect and enhances myelination in the prefrontal cortex of chronic restraint stress mice

  • Neuroscience. 2023 Nov 3:S0306-4522(23)00487-6. doi: 10.1016/j.neuroscience.2023.10.025.
Jin Zhang 1,  Weifen Li 2,  Qi Yue 3,  Luping Liu 4,  Sheng-Tao Hou 5,  Jun Ju 6
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Xi'an Medical University, Xi'an, China; State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China.
  • 2 State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen, China.
  • 3 Brain Research Centre and Department of Biology, Southern University of Science and Technology, Shenzhen, China; Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 4 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
  • 5 Brain Research Centre and Department of Biology, Southern University of Science and Technology, Shenzhen, China. Electronic address: houst@sustech.edu.cn.
  • 6 Brain Research Centre and Department of Biology, Southern University of Science and Technology, Shenzhen, China. Electronic address: juj@sustech.edu.cn.
PMID: 37926147 DOI: 10.1016/j.neuroscience.2023.10.025
Abstract

Depressive disorder is a psychiatric condition that is characterized by the core symptoms of anhedonia and learned helplessness. Myelination loss was recently found in the prefrontal cortex (PFC) of patients with depression and animal models, but the mechanism of this loss is unclear. In our previous study, chronic restraint stress (CRS) mice showed depressive-like symptoms. In this study, we found that myelin was reduced in the PFC of CRS mice. We also observed increased mammalian target of rapamycin (mTOR) phosphorylation levels in the PFC. Chronic injections of rapamycin, a mTOR complex inhibitor, prevented depressive behavior as shown by the forced swimming test and sucrose preference test. Rapamycin also increased myelination in the PFC of CRS mice. In summary, we found that CRS enhanced mTOR signaling and reduced myelination in the PFC and that rapamycin could prevent it. Our study provides the etiology of reduced myelin in depressive symptoms and suggests that mTOR signaling could be a target for treating depression or improving myelination deficits in depressive disorders.

Keywords

Depressive disorder; mTOR signaling; myelination; prefrontal cortex; rapamycin.

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