Dysregulated CRTC1-BDNF signaling pathway in the hippocampus contributes to A β oligomer-induced long-term synaptic plasticity and memory impairment

In this study, electrophysiological recordings indicated that lentivirus-mediated CRTC1 overexpression effectively ameliorates suppression of late-phase long-term potentiation (L-LTP) in rat hippocampal slices treated with oligomeric amyloid β(1-42) peptides (oAβ42) (200 nM). In addition, application of oAβ42 and genetic knockdown of CRTC1 by lentivirus-mediated CRTC1-shRNA inhibits L-LTP, whereas their combination does not further impair L-LTP. Brain-derived neurotrophic factor (BDNF), an important downstream protein confers protection of CRTC1 overexpression against oAβ42-induced L-LTP impairment as shown by administration of K252a (200 nM) and TrkB-FC (20 μg/mL). Furthermore, behavioral and western blotting analyses showed that CRTC1 overexpression reverses oAβ42-induced hippocampal-dependent cognitive deficits, downregulation of CRTC1 and BDNF expression. Notably, CRTC1-shRNA directly elicits cognitive deficits. In summary, these findings show that hippocampal CRTC1 signaling is affected by soluble oAβ, and CRTC1-BDNF pathway is involved in hippocampal L-LTP impairment and memory deficits induced by oAβ42.PMID:34274327 | DOI:10.1016/j.expneurol.2021.113812

Source: Experimental Neurology - July 18, 2021 Category: Neurology Authors: Peiyun Yan Zhancheng Xue Dezhu Li Saiqi Ni Chuang Wang Xinchun Jin Dongsheng Zhou Xingxing Li Xin Zhao Xiaowei Chen Wei Cui Dingli Xu Wenhua Zhou Junfang Zhang Source Type: research