2. Academic Validation
  3. Downregulated NT-3 and PI3K/AKT signaling pathway mediates arsenic-induced apoptosis in hippocampal neurons in vivo and in vitro

Downregulated NT-3 and PI3K/AKT signaling pathway mediates arsenic-induced apoptosis in hippocampal neurons in vivo and in vitro

  • Ecotoxicol Environ Saf. 2025 Jul 1:299:118372. doi: 10.1016/j.ecoenv.2025.118372.
Jia Cui 1,  Ziqiao Guan 1,  Xinbo Ma 1,  Xinhua Shao 1,  Kunyu Zhang 1,  Man Lv 1,  Meichen Zhang 1,  Xiaona Liu 1,  Yanhui Gao 2,  Yanmei Yang 3
Affiliations

Affiliations

  • 1 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin, Heilongjiang 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University Xi'an Jiaotong University), Harbin, Heilongjiang 150081, China.
  • 2 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin, Heilongjiang 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University Xi'an Jiaotong University), Harbin, Heilongjiang 150081, China. Electronic address: gaoyanhui@hrbmu.edu.cn.
  • 3 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin, Heilongjiang 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University, Guizhou Medical University Xi'an Jiaotong University), Harbin, Heilongjiang 150081, China. Electronic address: yangyanmei@hrbmu.edu.cn.
PMID: 40440981 DOI: 10.1016/j.ecoenv.2025.118372
Abstract

Arsenic is a neurotoxin associated with cognitive impairment following long-term exposure, while Neurotrophin-3 (NT-3) is essential for the survival and development of neurons. This study aims to explore the protective effects of NT-3 on arsenic-caused cognitive impairment and neuronal damage, as well as clarify the underlying mechanisms. In vivo and in vitro results indicated that sodium arsenite impaired cognitive function, reduced neuronal density, and induced Apoptosis, which was accompanied by the down-regulation of NT-3 and the PI3K/Akt pathway. Overexpression of NT-3 in HT-22 cells mitigated Apoptosis triggered by arsenic and partially restored PI3K/Akt pathway activity. Thus, our findings suggest that NT-3 may counteract the arsenic neurotoxicity by activating PI3K/Akt.

Keywords

Apoptosis; Arsenic; Hippocampal neuron; NT-3; PI3K/AKT.

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