1. Academic Validation
  2. Fluoride Stimulates Anxiety- and Depression-like Behaviors Associated with SIK2-CRTC1 Signaling Dysfunction

Fluoride Stimulates Anxiety- and Depression-like Behaviors Associated with SIK2-CRTC1 Signaling Dysfunction

  • J Agric Food Chem. 2021 Nov 17;69(45):13618-13627. doi: 10.1021/acs.jafc.1c04907.
Guoyu Zhou 1 Yue Hu 1 Anqi Wang 1 Meng Guo 1 Yuhui Du 1 Yongxiang Gong 1 Limin Ding 1 Zichen Feng 1 Xiangbo Hou 1 Kaihong Xu 1 Fangfang Yu 1 Zhiyuan Li 1 Yue Ba 1
Affiliations

Affiliation

  • 1 Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.
Abstract

Using Sprague-Dawley rats and rat PC12 cells treated with sodium fluoride (NaF), we investigated the effects of SIK2-CRTC1 signaling on the neurobehavioral toxicity induced by fluoride. The in vivo results demonstrated that NaF treatment induced anxiety- and depression-like behaviors in juvenile rats, resulting in histological and ultrastructural abnormalities in the rat hippocampus and medial prefrontal cortex. Moreover, NaF exposure induced neuronal loss and excessive Apoptosis. We also found that NaF elevated the expression of SIK2 and reduced the expression of CRTC1, brain-derived neurotrophic factor (BDNF), and VGF. The in vitro results showed that NaF suppressed cell viability, induced SIK2-CRTC1 signaling dysfunction, and caused excessive Apoptosis in PC12 cells. Notably, targeted knockout of SIK2 with SIK2-siRNA or blocking of SIK2-CRTC1 signaling with 7,8-dihydroxyflavone (7,8-DHF) (as well as venlafaxine) can reduce Apoptosis and increase cell viability in vitro. These findings suggest that neuronal death resulting from abnormal SIK2-CRTC1 signaling contributes to neurobehavioral toxicity induced by fluoride.

Keywords

SIK2; anxiety; depression; fluoride; rat.

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