Suicide in bipolar disorder patients is associated with hippocampal microglia activation and reduction of lymphocytes-activation gene 3 (LAG3) microglial checkpoint expression.
Brain Behav Immun
; 110: 185-194, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36863492
ABSTRACT
BACKGROUND:
Bipolar disorder (BD) is associated with marked functional impairments along with increased rate of suicide. Although there is ample evidence for the involvement of inflammatory processes and microglia activation in the pathophysiology of BD, the mechanisms that regulate these cells in BD patients, and particularly the role of microglia checkpoints, is still unclear.METHODS:
Immunohistochemical analyses of hippocampal sections from post-mortem brains of 15 BD patients and 12 control subjects were used to assess microglia density, by staining the microglia-specific receptor P2RY12, and microglia activation, by staining the activation marker MHC II. Given recent findings on the involvement of LAG3, which interacts with MHC II and serves as a negative microglia checkpoint, in depression and electroconvulsive therapy, we assessed the levels of LAG3 expression and their correlations with microglia density and activation.RESULTS:
There were no overall differences between BD patients and controls, but BD patients who committed suicide (N = 9) displayed a significant elevation in the overall microglia density and the density of MHC II-labeled microglia (but not other MHC II-labeled cells), compared with no suicide BD patients (N = 6) and controls. Furthermore, the percent of microglia expressing LAG3 was significantly reduced only in suicidal BD patients, with significant negative correlations between microglial LAG3 expression levels and the density of microglia, in general, and activated microglia, in particular.CONCLUSION:
Suicidal BD patients exhibit microglia activation, which is possibly mediated by reduced LAG3 checkpoint expression, suggesting that anti-microglial therapeutics, including LAG3 modulators, may be beneficial for this subgroup of patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Suicídio
/
Transtorno Bipolar
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Brain Behav Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Israel