Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity

Little is known about age-dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age-dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis...

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Detalles Bibliográficos
Autores: Popov, Alexander, Brazhe, Alexey, Denisov, Pavel, Sutyagina, Oksana, Li, Li, Lazareva, Natalia, Verkhratsky, Alexei, Semyanov, Alexey
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/50765
Acceso en línea:http://hdl.handle.net/10810/50765
Access Level:acceso abierto
Palabra clave:K+ buffering
ageing
astrocytic complexity
astrocytic cradle
glutamate uptake
perisynaptic astrocytic processes
Descripción
Sumario:Little is known about age-dependent changes in structure and function of astrocytes and of the impact of these on the cognitive decline in the senescent brain. The prevalent view on the age-dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two-photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis, we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains andin astrocyte-to-astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch clamp, and Ca2+ imaging revealed deficits in K+ and glutamate clearance and spatiotemporal reorganisation of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long-term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain the astroglial mechanisms of age-dependent decline in learning and memory.