Integrating spatial and single-nucleus transcriptomic data elucidates microglial-specific responses in female cynomolgus macaques with depressive-like behaviors.
Nat Neurosci
; 26(8): 1352-1364, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-37443281
ABSTRACT
Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we profile the dorsolateral prefrontal cortex of female cynomolgus macaques with social stress-associated depressive-like behaviors using single-nucleus RNA-sequencing and spatial transcriptomics. We find gene expression changes associated with depressive-like behaviors mostly in microglia, and we report a pro-inflammatory microglia subpopulation enriched in the depressive-like condition. Single-nucleus RNA-sequencing data result in the identification of six enriched gene modules associated with depressive-like behaviors, and these modules are further resolved by spatial transcriptomics. Gene modules associated with huddle and sit alone behaviors are expressed in neurons and oligodendrocytes of the superficial cortical layer, while gene modules associated with locomotion and amicable behaviors are enriched in microglia and astrocytes in mid-to-deep cortical layers. The depressive-like behavior associated microglia subpopulation is enriched in deep cortical layers. In summary, our findings show cell-type and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behaviors in female non-human primates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microglia
/
Transtorno Depressivo Maior
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China