• Yang Zhu, Min Gao, Hao Huang, Shi-Hao Gao, Ling-Yi Liao, Yong Tao, Huan Cheng, and Chang-Yue Gao.
• Department of Neurology, Daping Hospital, Army Medical University, 10 Changjiang Branch Road, Yu-Zhong District, 400042 Chongqing, China.
• Neuroscience. 2022 Aug 1; 496: 27-37.

AbstractThe neurotrophin receptor p75 (p75NTR) is a circadian rhythm regulator and mediates cognitive deficits induced by sleep deprivation (SD). The soluble extracellular domain of p75NTR (p75ECD) has been shown to exert a neuroprotective function in Alzheimer's disease (AD) and depression animal models. Nevertheless, the role of p75ECD in SD-induced cognitive dysfunction is unclear. In the present study we administrated p75ECD-Fc (10, 3 mg/kg), a recombinant fusion protein of human p75ECD and fragment C of immunoglobulin IgG1, to treat mice via intraperitoneal injection. The results revealed that peripheral supplementation of high-dose p75ECD-Fc (10 mg/kg) recovered the balance between Aβ and p75ECD in the hippocampus and rescued the cognitive deficits in SD mice. We also found that p75ECD-Fc ameliorated other pathologies induced by SD, including neuronal apoptosis, synaptic plasticity impairment and neuroinflammation. The current study suggests that p75ECD-Fc is a potential candidate for SD and peripheral supplementation of p75ECD-Fc may be a prospective preventive measure for cognitive decline in SD.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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