Hippocampal microglia CD40 mediates NPSLE cognitive dysfunction in mice.
J Neuroimmunol
; 357: 577620, 2021 08 15.
Article
em En
| MEDLINE
| ID: mdl-34062352
ABSTRACT
Neuropsychiatric systemic lupus erythematosus (NPSLE) is the most serious and complicated clinical manifestation of lupus erythematosus. Cognitive dysfunction is the most common symptom of NPSLE. A variety of potential mechanisms or mediators related to the pathogenesis of NPSLE cognitive dysfunction have been proposed. However, the involvement of microglia CD40 has not been reported yet. This study aimed to investigate whether hippocampal microglia CD40 of MRL/MpJ-Faslpr (MRL/lpr) mice was involved in NPSLE cognitive dysfunction. This study found, using quantitative polymerase chain reaction, western blotting and immunohistochemistry, that hippocampal CD40 was aberrantly overexpressed in the MRL/lpr lupus mice. It also determined using flow cytometry and immunofluorescence that the aberrantly overexpressed CD40 was mainly derived from hippocampal microglia. The adeno-associated virus was used to inhibit microglia CD40 expression, and the brain damage and cognitive dysfunction of MRL/lpr mice improved. Also, imiquimod (IMQ)-induced lupus mice had the same NPSLE cognitive dysfunction, brain damage, and overexpressed hippocampal microglia CD40 as MRL/lpr mice. Therefore, IMQ-induced lupus mouse was proposed as one of the mouse models for studying NPSLE cognitive dysfunction for the first time in this study. The findings indicated that hippocampal microglia CD40 was involved in the development of NPSLE cognitive dysfunction, thus providing a novel research direction for the study of the pathogenesis of NPSLE.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
4_TD
Problema de saúde:
4_meningitis
Assunto principal:
Microglia
/
Antígenos CD40
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Vasculite Associada ao Lúpus do Sistema Nervoso Central
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Disfunção Cognitiva
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Hipocampo
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China