Retrosplenial cortex microglia and perineuronal net densities are associated with memory impairment in aged rhesus macaques.
Cereb Cortex
; 33(8): 4626-4644, 2023 04 04.
Article
en En
| MEDLINE
| ID: mdl-36169578
ABSTRACT
Synapse loss and altered plasticity are significant contributors to memory loss in aged individuals. Microglia, the innate immune cells of the brain, play critical roles in maintaining synapse function, including through a recently identified role in regulating the brain extracellular matrix. This study sought to determine the relationship between age, microglia, and extracellular matrix structure densities in the macaque retrosplenial cortex. Twenty-nine macaques ranging in age from young adult to aged were behaviorally characterized on 3 distinct memory tasks. Microglia, parvalbumin (PV)-expressing interneurons and extracellular matrix structures, known as perineuronal nets (PNNs), were immuno- and histochemically labeled. Our results indicate that microglia densities increase in the retrosplenial cortex of aged monkeys, while the proportion of PV neurons surrounded by PNNs decreases. Aged monkeys with more microglia had fewer PNN-associated PV neurons and displayed slower learning and poorer performance on an object recognition task. Stepwise regression models using age and the total density of aggrecan, a chondroitin sulfate proteoglycan of PNNs, better predicted memory performance than did age alone. Together, these findings indicate that elevated microglial activity in aged brains negatively impacts cognition in part through mechanisms that alter PNN assembly in memory-associated brain regions.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Microglía
/
Giro del Cíngulo
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cereb Cortex
Asunto de la revista:
CEREBRO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos