Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease.
Neural Regen Res
; 17(9): 2079-2088, 2022 Sep.
Article
en En
| MEDLINE
| ID: mdl-35142700
ABSTRACT
Regular exercise has been shown to reduce the risk of Alzheimer's disease (AD). Our previous study showed that the protein aquaporin 4 (AQP4), which is specifically expressed on the paravascular processes of astrocytes, is necessary for glymphatic clearance of extracellular amyloid beta (Aß) from the brain, which can delay the progression of Alzheimer's disease. However, it is not known whether AQP4-regulated glymphatic clearance of extracellular Aß is involved in beneficial effects of exercise in AD patients. Our results showed that after 2 months of voluntary wheel exercise, APP/PS1 mice that were 3 months old at the start of the intervention exhibited a decrease in Aß burden, glial activation, perivascular AQP4 mislocalization, impaired glymphatic transport, synapse protein loss, and learning and memory defects compared with mice not subjected to the exercise intervention. In contrast, APP/PS1 mice that were 7 months old at the start of the intervention exhibited impaired AQP4 polarity and reduced glymphatic clearance of extracellular Aß, and the above-mentioned impairments were not alleviated after the 2-month exercise intervention. Compared with age-matched APP/PS1 mice, AQP4 knockout APP/PS1 mice had more serious defects in glymphatic function, Aß plaque deposition, and cognitive impairment, which could not be alleviated after the exercise intervention. These findings suggest that AQP4-dependent glymphatic transport is the neurobiological basis for the beneficial effects of voluntary exercises that protect against the onset of AD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
Problema de salud:
1_doencas_transmissiveis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Neural Regen Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
China