Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders.
Int Immunopharmacol
; 113(Pt B): 109436, 2022 Dec.
Article
in English
| MEDLINE | ID: covidwho-2119471
ABSTRACT
Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib (PLX3397) and social isolation. Herein, we adopted PLX3397 to investigate the role of microglia in the modulation of social isolation. Our results found that social isolation during adolescence caused depressive-like, but not anxiety-like behavior in mice in adulthood, with enhanced expression of the microglial marker Iba1 in the hippocampus. In addition, treatment with PLX3397 reduced the expression of the microglial marker Iba1, decreased the mRNA expression of IL-1ß, increased the mRNA expression of Arg1, elevated the protein levels of DCX and GluR1 and restored the dendritic spine branches and density, ultimately mitigating depressive-like behavior in mice. These findings suggest that inhibition of microglia in the hippocampus could ameliorate mood disorders in mice, providing a new perspective for the treatment of psychiatric disorders such as depression.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Mood Disorders
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Int Immunopharmacol
Journal subject:
Allergy and Immunology
/
Pharmacology
Year:
2022
Document Type:
Article
Affiliation country:
J.intimp.2022.109436
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