2. Academic Validation
  3. Histone hypoacetylation contributes to neurotoxicity induced by chronic nickel exposure in vivo and in vitro

Histone hypoacetylation contributes to neurotoxicity induced by chronic nickel exposure in vivo and in vitro

  • Sci Total Environ. 2021 Aug 20:783:147014. doi: 10.1016/j.scitotenv.2021.147014.
Chao Zhou 1,  Mengyu Liu 2,  Xiang Mei 1,  Qian Li 3,  Wenjuan Zhang 1,  Ping Deng 1,  Zhixin He 1,  Yu Xi 4,  Tong Tong 4,  Huifeng Pi 1,  Yonghui Lu 1,  Chunhai Chen 1,  Lei Zhang 1,  Zhengping Yu 5,  Zhou Zhou 6,  Mindi He 7
Affiliations

Affiliations

  • 1 Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China.
  • 2 Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China; Department of Medical Laboratory, General Hospital of the Central Theater Command of the Chinese People's Liberation Army, 430070 Wuhan, People's Republic of China.
  • 3 Department of Otolaryngology Head and Neck Surgery, Xinqiao Hospital, Army Medical University, 400037 Chongqing, People's Republic of China.
  • 4 Department of Environmental Medicine, School of Public Health, Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, People's Republic of China.
  • 5 Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China. Electronic address: [email protected].
  • 6 Department of Environmental Medicine, School of Public Health, Department of Emergency Medicine, First Affiliated Hospital, School of Medicine, Zhejiang University, 310058 Hangzhou, People's Republic of China. Electronic address: [email protected].
  • 7 Department of Occupational Health, Army Medical University, 400038 Chongqing, People's Republic of China. Electronic address: [email protected].
PMID: 34088129 DOI: 10.1016/j.scitotenv.2021.147014
Abstract

Nickel (Ni) is a heavy metal that is both an environmental pollutant and a threat to human health. However, the effects of Ni on the central nervous system in susceptible populations have not been well established. In the present study, the neurotoxicity of Ni and its underlying mechanism were investigated in vivo and in vitro. Ni exposure through drinking water (10 mg Ni/L, 12 weeks) caused learning and memory impairment in mice. Reduced dendrite complexity was observed in both Ni-exposed mouse hippocampi and Ni-treated (200 μM, 72 h) primary cultured hippocampal neurons. The levels of histone acetylation, especially at histone H3 lysine 9 (H3K9ac), were reduced in Ni-exposed mouse hippocampi and cultured neurons. RNA Sequencing and chromatin immunoprecipitation (ChIP) Sequencing analyses revealed that H3K9ac-modulated gene expression were downregulated. Treatment with sodium butyrate, a histone deacetylase inhibitor, attenuated Ni-induced H3K9 hypoacetylation, neural gene downregulation and dendrite complexity reduction in cultured neurons. Sodium butyrate also restored Ni-induced memory impairment in mice. These results indicate that Ni-induced H3K9 hypoacetylation may be a contributor to the neurotoxicity of Ni. The finding that Ni disturbs histone acetylation in the nervous system may provide new insight into the health risk of chronic Ni exposure.

Keywords

ChIP-seq; Cognitive deficits; Dendrite complexity; Histone acetylation; Ni; RNA-seq.

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