Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence.
PLoS Biol
; 22(4): e3002559, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38652714
ABSTRACT
Increasing evidence indicates that terminally differentiated neurons in the brain may recommit to a cell cycle-like process during neuronal aging and under disease conditions. Because of the rare existence and random localization of these cells in the brain, their molecular profiles and disease-specific heterogeneities remain unclear. Through a bioinformatics approach that allows integrated analyses of multiple single-nucleus transcriptome datasets from human brain samples, these rare cell populations were identified and selected for further characterization. Our analyses indicated that these cell cycle-related events occur predominantly in excitatory neurons and that cellular senescence is likely their immediate terminal fate. Quantitatively, the number of cell cycle re-engaging and senescent neurons decreased during the normal brain aging process, but in the context of late-onset Alzheimer's disease (AD), these cells accumulate instead. Transcriptomic profiling of these cells suggested that disease-specific differences were predominantly tied to the early stage of the senescence process, revealing that these cells presented more proinflammatory, metabolically deregulated, and pathology-associated signatures in disease-affected brains. Similarly, these general features of cell cycle re-engaging neurons were also observed in a subpopulation of dopaminergic neurons identified in the Parkinson's disease (PD)-Lewy body dementia (LBD) model. An extended analysis conducted in a mouse model of brain aging further validated the ability of this bioinformatics approach to determine the robust relationship between the cell cycle and senescence processes in neurons in this cross-species setting.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Envejecimiento
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Ciclo Celular
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Senescencia Celular
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Enfermedad de Alzheimer
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Neuronas
Límite:
Aged
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Animals
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Humans
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Male
Idioma:
En
Revista:
PLoS Biol
Asunto de la revista:
BIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China