Effect of fluoride exposure on anxiety- and depression-like behavior in mouse

Chemosphere. 2019 Jan;215:454-460. doi: 10.1016/j.chemosphere.2018.10.070. Epub 2018 Oct 13.


We established the mouse model of fluoride (68 mg F ion/L deionized water) exposure for 90 days, 120 days and 150 days, and applied diverse methods as behavioral models of anxiety and depression, and analyzed the levels of the anxiety- and depression-like related genes like BDNF1, BDNF4, 5-HT1A, VGLUT, GAD67, and VGAT in the mouse hippocampus. In the mice exposed to NaF for 120 days, compared to the control group, chalky opacity was observed on the enamel of teeth; the results of anxiety-like behavior, like elevated zero maze, light/dark exploration test, novel object recognition test and emergence test were significantly altered, however in the mice exposed for 150 days, only the elevated zero maze and emergence test were significantly altered. Also, the results of depression-like behavior were significantly altered in the 120 days treated mice. Exposure to NaF for 120 days significantly decreased the mRNA expression levels of the BDNF4 with a concomitant increase in the 5-HT1A compared to the control mice. Especially the mRNA expression levels of GAD67 and VGAT were significantly decreased in all the three NaF treated groups. However, no significant changes were observed in the mRNA expression levels of the VGLUT compared to the control mice. In summary, we speculated that fluoride exposure had adverse effects on nervous system, inducing an imbalance between excitation and inhibition, which resulted in abnormal behavior and depression.

Keywords: Anxiety; Depression; Fluoride; Hippocampus; Mouse.

MeSH terms

  • Animals
  • Anxiety / chemically induced*
  • Anxiety / metabolism
  • Behavior, Animal / drug effects*
  • Brain-Derived Neurotrophic Factor / genetics
  • Depression / chemically induced*
  • Depression / metabolism
  • Fluorides / toxicity*
  • Glutamate Decarboxylase / genetics
  • Hippocampus / metabolism
  • Mice
  • Phosphates
  • RNA, Messenger / metabolism
  • Serotonin / genetics
  • Vesicular Inhibitory Amino Acid Transport Proteins / genetics


  • Brain-Derived Neurotrophic Factor
  • Phosphates
  • RNA, Messenger
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • fluorophosphate
  • Serotonin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Fluorides