Details

Autor(en) / Beteiligte

• Zhang, Wanning
• Chen, Xinyue
• Du, Zunshu
• Mao, Xin
• Gao, Ruiqi
• Chen, Ziyan
• Wang, Hongqi
• Zhang, Guitao
• Zhang, Ning
• Li, Hui
• Song, Yizhi
• Chang, Lirong
• Wu, Yan

Titel

Knockdown of astrocytic Grin2a exacerbated sleep deprivation-induced cognitive impairments and elevation of amyloid-beta

Ist Teil von

• Sleep medicine, 2022-12, Vol.100, p.280-290

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Sleep disorders are associated with cognitive impairments, greater amyloid-β (Aβ) burden and increased risk of developing Alzheimer’s disease, while the underlying mechanism is unclear. N-methyl-d-aspartate receptors (NMDARs), as vital modulators of cognition, are sensitive to sleep disturbance. Sleep deprivation (SD) could induce the alterations of neuronal NMDAR subunits expression, however the alterations of astrocytic NMDARs in SD have not been reported. Our previous study has demonstrated knockdown of astrocytic Grin2a (gene encoding NMDAR subunit GluN2A) could aggravate Aβ-induced cognitive impairments, but what role astrocytic GluN2A may play in SD is unknown. Here we focused on the changes and roles of hippocampal astrocytic GluN2A in SD. Our results showed SD increased the expression of astrocytic GluN2A. Specific knockdown of hippocampal astrocytic Grin2a aggravated SD-induced cognitive decline, elevated Aβ, and attenuated the SD-induced increase in autophagy flux. Our finding, for the first time, revealed a novel neuroprotective role for astrocytic GluN2A in SD, which may be helpful for developing new preventive and therapeutic targets to sleep disorders. •Sleep deprivation induced the increase of astrocytic GluN2A expression in the hippocampus.•Knockdown of hippocampal astrocytic Grin2a exacerbated sleep deprivation-induced cognitive impairments.•Knockdown of hippocampal astrocytic Grin2a aggravated sleep deprivation-induced elevation of amyloid-beta1-42 level.•Knockdown of hippocampal astrocytic Grin2a attenuated sleep deprivation-induced increase in autophagy flux.