miR146a reduces depressive behavior by inhibiting microglial activation.
Mol Med Rep
; 23(6)2021 06.
Article
em En
| MEDLINE
| ID: mdl-33880591
ABSTRACT
Depression is one of the major psychiatric diseases affecting the quality of life for individuals worldwide. Numerous reports have investigated depression, although its etiology remains to be elucidated. microRNA (miR)146a is suggested to regulate innate immune and inflammatory responses. However, it is unclear whether miR146a is involved in depression. Depression model mice were established using lipopolysaccharideinduced depression and chronic unpredictable mild stress, separately. miR146a mimic and short interfering RNA were used to treat depressed mice. Depressionlike behaviors and levels of proinflammatory cytokines were measured, while ionized calcium binding adapter molecule 1 (Iba1) expression in hippocampus was quantified by immunohistochemistry. Neuroinflammatory factor levels in hippocampus were measured by western blotting. BV2 cells were used to confirm that miR146a suppressed microglia activation. Compared with control mice, the two depressed mouse models showed clearly decreased sucrose preference and significantly increased immobility time in the forced swimming test and tail suspension test (P<0.05). miR146a overexpression significantly increased sucrose preference and reduced immobility time in depressed mice (P<0.05). However, total distance traveled in the locomotor activity test did not differ among groups. Compared with controls, expression levels of Iba1, inducible nitric oxide, IL1ß, TNFα, interleukin 1 receptor associated kinase 1 (IRAK1), TNF receptorassociated factor 6 (TRAF6) and phosphorylated NFκB p65 were significantly increased in depressed mice (P<0.05). miR146a overexpression effectively inhibited expression of these neuroinflammatory proteins, while miR146a silencing significantly upregulated their expression (P<0.05). Consistent with these in vivo results, miR146a mimic treatment inhibited TNFα, IL1ß, IRAK1 and TRAF6 expression in BV2 cells. miR146a improved depressive behaviors in depressed model mice by inhibiting microglial activation and neuroinflammatory factor expression.
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Base de dados:
MEDLINE
Assunto principal:
Microglia
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MicroRNAs
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Depressão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2021
Tipo de documento:
Article