2. Academic Validation
  3. Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors

Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors

  • Brain Res Bull. 2022 Jul;185:91-98. doi: 10.1016/j.brainresbull.2022.05.004.
Xiang-Fei Guo 1,  Xin-Hao Wang 1,  Ya-Ling Fu 1,  Qian Meng 1,  Bo-Ya Huang 1,  Rui Yang 1,  Yi Guo 1,  Yu-Ru Du 1,  Xi Wang 1,  Yuan Gao 1,  Li Song 1,  Miao Gong 2,  Sheng Wang 1,  You-Dong Li 3,  Hai-Shui Shi 4,  Yun Shi 5
Affiliations

Affiliations

  • 1 Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key laboratory of Neurophysiology, Hebei Medical University, 050017, China.
  • 2 Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Experimental Center for Teaching, Hebei Medical University, Shijiazhuang 050017, China.
  • 3 Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
  • 4 Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key laboratory of Neurophysiology, Hebei Medical University, 050017, China. Electronic address: [email protected].
  • 5 Neuroscience Research Center, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China; Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education of China, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: [email protected].
PMID: 35550155 DOI: 10.1016/j.brainresbull.2022.05.004
Abstract

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that Epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

Keywords

Anxiety; Depression; Hippocampus; N-acetyltransferase 10; Neuron.

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