期刊
BEHAVIOURAL BRAIN RESEARCH
卷 417, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbr.2021.113594
关键词
Calpain; Fear memory; Piezo1; Sleep deprivation; TrkB
资金
- National Natural Science Foundation of China (NSFC) [81271203]
- CPLA Youth Training Project for Medical Science [21QNPY098, 20QNPY065, 17QNP030]
- Hospital Youth Innovation Fund
The study demonstrated that the Piezo1/Ca2+/calpain pathway in the basal forebrain modulates impaired fear conditioning caused by sleep deprivation. Activation or inhibition of Piezo1 protein can affect the cleavage of TrkB and fear memory in rats under sleep deprivation conditions.
In this study, we tested the hypothesis that the Piezo1/Ca2+/calpain pathway of the basal forebrain (BF) modulates impaired fear conditioning caused by sleep deprivation. Adult male Wistar rats were subjected to 6 h of total sleep deprivation using the gentle handling protocol. Step-down inhibitory avoidance tests revealed that sleep deprivation induced substantial short- and long-term fear memory impairment in rats, which was accompanied by increased Piezo1 protein expression (P < 0.01) and increased cleavage of full-length tropomyocin receptor kinase B (TrkB-FL) (P < 0.01) in the BF area. Microinjection of the Piezo1 activator Yoda1 into the BF mimicked these sleep deprivation-induced phenomena; TrkB-FL cleavage was increased (P < 0.01) and short- and long-term fear memory was impaired (both P < 0.01) by Yoda1. Inhibition of Piezo1 by GsMTx4 in the BF area reduced TrkB-FL degradation (P < 0.01) and partially reversed short- and long-term fear memory impairments in sleep-deprived rats (both P < 0.01). Inhibition of calpain activation, downstream of Piezo1 signaling, also improved short- and long-term fear memory impairments (P = 0.038, P = 0.011) and reduced TrkB degradation (P < 0.01) in sleep-deprived rats. Moreover, sleep deprivation induced a lower pain threshold than the rest control, which was partly reversed by microinjection of GsMTx4 or PD151746. Neither sleep deprivation nor the abovementioned drugs affected locomotion and sedation. Taken together, these results indicate that BF Piezo1/Ca2+/calpain signaling plays a role in sleep deprivation-induced TrkB signaling disruption and fear memory impairments in rats.
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