The Mechanism Underlying Cadmium Exposure Inhibits Adult Neurogenesis And Working Memory In Mice Through SOCE Pathway

Background: Cadmium is a toxic heavy metal,widely present in the environment and easy to accumulate in the body.Its neurotoxicity is closely related to cognitive impairment in children and middle-aged and elderly people,but underlying mechanism is not clear.Studying the mechanism of cadmium-induced cognitive impairment is crucial to prevent and improve cognitive decline caused by cadmium exposure.Objective: To explore the underlying mechanism the impairment of induced adult neurogenesis and working memory in mice exposed to cadmium,thus providing therapy targets for preventing and improving cognitive impairment caused by cadmium exposure.Methods: Human neuroblastoma cells(SH-SY5Y)and C57BL/6J mice were used as experimental subjects.The effects of cadmium exposure on the proliferation of SHSY5 Y cells and the proliferation of mouse hippocampal neural stem cells were detected by Brd U fluorescence labeling.Brd U,DCX and Neu N fluorescence labeling were used to detect adult hippocampal neurogenesis in mice.The effects of cadmium exposure on cognition and spontaneous motor ability of mice were detected by open field and Y maze experiments.The intracellular calcium signal of SH-SY5 Y cells was detected by Fluo-3AM,and the intracellular enrichment of cadmium exposed cells was detected by Leadmiuum Green AM Dye and ER-Tracker Rad.The expression levels of SOCE signaling proteins in SH-SY5 Y cells were detected by immunofluorescence.Western Blot was used to detect the expression of SOCE calcium signaling proteins in hippocampus of mice.Results: 1)Cadmium exposure inhibited hippocampal adult neurogenesis in C57 BL / 6J mice,and the morphological structure and number of newborn neurons in cadmium exposed mice were abnormal;2)Cadmium exposure impaired working memory in C57BL/6J mice;3)Cadmium exposure inhibited the proliferation of SH-SY5 Y cells;4)Cadmium exposure inhibited SOCE channel and induced calcium overload in SHSY5 Y cells;5)Activated SOCE channel can reverse the inhibitory effect of cadmium exposure on the proliferation of SH-SY5 Y cells.Conclusion: Cadmium exposure may cause intracellular calcium overload by inhibiting the SOCE calcium signaling pathway,thus inhibiting the proliferation of neural stem cells and adult neurogenesis and eventually leading to cognitive impairment.