1. Academic Validation
  2. Activation of α7nAChR by PNU282987 improves cognitive impairment through inhibiting oxidative stress and neuroinflammation in D-galactose induced aging via regulating α7nAChR/Nrf2/HO-1 signaling pathway

Activation of α7nAChR by PNU282987 improves cognitive impairment through inhibiting oxidative stress and neuroinflammation in D-galactose induced aging via regulating α7nAChR/Nrf2/HO-1 signaling pathway

  • Exp Gerontol. 2023 Mar 10;175:112139. doi: 10.1016/j.exger.2023.112139.
Yawen Zhang 1 Rui Ma 1 Wencheng Wang 2 Qian Deng 1 Chi Cao 1 Chunyang Yu 1 Shulin Li 1 Lei Shi 1 Jianying Tian 3
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
  • 2 People's Hospital of Ningxia Hui Autonomous region, Yinchuan 750002, China.
  • 3 School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China. Electronic address: NYTianjianying@163.com.
Abstract

Aging is an important risk factor for neurodegenerative diseases. The activation of α7 nicotinic acetylcholine receptor (α7nAChR) is involved in inflammation and cognition, but the specific role it plays in aging remains unknown. This study aimed to investigate the Anti-aging effect of the activation of α7nAChR on aging rats and BV2 cells induced by D-galactose, as well as its potential mechanism. D-galactose induced an increase in the SA-β-Gal positive cells, expression of p16 and p21 in vivo and in vitro. α7nAChR selective agonist PNU282987 decreased levels of pro-inflammatory factors, MDA, and Aβ, enhanced SOD activity and levels of anti-inflammatory factor (IL10) in vivo. PNU282987 enhanced the expression of Arg1, decreased the expression of iNOS, IL1β and TNFα in vitro. PNU282987 upregulated the levels of α7nAChR, Nrf2 and HO-1 in vivo and in vitro. The results of Morris water maze and novel object recognition tests showed that PNU282987 improved cognitive impairment in aging rats. Furthermore, α7nAChR selective inhibitor methyllycaconitine (MLA) results were opposite with PNU282987. PNU282987 improves cognitive impairment through inhibiting oxidative stress and neuroinflammation in D-galactose induced aging via regulating the α7nAChR/Nrf2/HO-1 signaling pathway. Therefore, targeting the α7nAChR may be a viable therapeutic approach for anti-inflammaging and neurodegenerative diseases.

Keywords

Aging; Microglia; Neuroinflammation; Oxidative stress; α7nAChR.

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