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An early increase in glutamate is critical for the development of depression-like behavior in a chronic restraint stress (CRS) model.
Metadata
Journalbrain research bulletin3.37Date
2020 Jun 04
4 months ago
Type
Journal Article
Volume
2020-Sep / 162 : 59-66
Author
Li J 1, Sha L 2, Xu Q 3
Affiliation
  • 2. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Neuroscience Center of Chinese Academy of Medical Sciences, China.
  • 3. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China; Neuroscience Center of Chinese Academy of Medical Sciences, China. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
Dysfunction in glutamate homeostasis contributes to the pathology of depression-like behavior. Using a chronic restraint stress (CRS) model of depression in C57BL/6 mice, we measured glutamate levels in the cerebrospinal fluid at different restraint time points (CRS 1 d, CRS 3 d, CRS 5 d, CRS 7 d, CRS 14 d, and CRS 21 d). Glutamate levels were increased in the early stage of stress (CRS 1 d and CRS 5 d) but returned to basal levels at the other time points (CRS 7 d-21 d). We hypothesized that glutamate-induced excitotoxicity is critical for the development of depression-like behavior in the CRS model. Treatment with sodium valproate (VPA) or lamotrigine (LTG), two drugs that prevent excitotoxicity in neurons by increasing inhibitory inputs or blocking sodium channels, in the early stage (CRS 1 d-5 d) was sufficient to correct depression-like behavior. In contrast, treatment with the classic antidepressant fluoxetine (FLX) during the same time period was not sufficient to correct depressive behavior. Western blot of two markers of dendritic spines PSD95 and VGluT1 showed that restraining mice for 5 d resulted in the loss of dendritic spines, which was rescued by VPA or LTG. In conclusion, an initial increase in glutamate levels plays an important role in the development of depression-like behavior in the CRS model.
Keywords: Cerebrospinal fluid (CSF) Chronic restraint stress (CRS) Depression Glutamate
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Brain Res Bullbrain research bulletin
Metadata
LocationUnited States
FromPERGAMON-ELSEVIER SCIENCE LTD

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