Abstract

It is known that fluorine and aluminum are commonly found in the environment and that long-term overexposure can adversely affect the organism’s nervous system, damaging the structure and function of brain tissue. Our previous study showed that fluorine combined with aluminum (FA) could trigger apoptosis in vitro and cause spatial learning and memory impairment and differentially expressed miRNAs (including miR-34b-5p) in the hippocampi in vivo. However, the detailed mechanism is unclear. Learning memory damage is implicated in excessive hippocampal neuron apoptosis, and miR-34b-5p participates in regulating the hippocampal neuron apoptosis. Thus, in the current research, Sprague-Dawley (SD) rats were subjected to FA, and NG108-15 control cells and NG108-15 cells pretransfected with miR-34b-5p agomir or antagomir were exposed to FA. We found that FA triggered apoptosis of rat hippocampal neurons and NG108-15 cells, increased miR-34b-5p expression, and decreased Gnai2, PKA, ERK and CREB expression. Inhibition of miR-34b-5p alleviated FA-induced NG108-15 cell apoptosis and further increased Gnai2, PKA, ERK, and CREB expression, and vice versa. Furthermore, miR-34b-5p modulated the level of Gnai2 by directly targeting its 3′-untranslated region (UTR), as verified through the dual Luciferase reporter assay. These outcomes suggested that miR-34b-5p participated in FA-induced neuronal apoptosis by targeting Gnai2 negatively, thereby inhibiting the PKA/ERK/CREB signaling pathway. Graphical Abstract