Protective effect of lithium chloride against hypoglycemia-induced apoptosis in neuronal PC12 cell

- We established a hypoglycemia model in neuronal PC12 cell.
- Hypoglycemia induced increased apoptosis in PC12 cell.
- Hypoglycemia significantly inhibits the gene/protein expressions of Wnt pathway.
- LiCl can attenuate hypoglycemia-induced apoptosis in PC12 cells via Wnt pathway.
- LiCl may be a therapy for reducing neurological damage caused by hypoglycemia.

Hypoglycemia is defined by an arbitrary plasma glucose level lower than 3.9 mmol/L and is a most common and feared adverse effect of treatment of diabetes mellitus. Emerging evidences demonstrated that hypoglycemia could induce enhanced apoptosis. Lithium chloride (LiCl), a FDA approved drug clinically used for treatment of bipolar disorders, is recently proven having neuroprotection against various stresses in the cellular and animal models of neural disorders. Here, we have established a hypoglycemia model in vitro and assessed the neuroprotective efficacy of LiCl against hypoglycemia-induced apoptosis and the underlying cellular and molecular mechanisms. Our studies showed that LiCl protects against hypoglycemia-induced neurotoxicity in vitro. Exposure to hypoglycemia results in enhanced apoptosis and the underlying cellular and molecular mechanisms involved inhibition of the canonical Wnt signaling pathway by decreasing wnt3a levels, β-catenin levels and increasing GSK-3β levels, which was confirmed by the use of Wnt-specific activator LiCl. Hypoglycemia-induced apoptosis were significantly reversed by LiCl, leading to increased cell survival. LiCl also alters the expression/levels of the Wnt pathway genes/proteins, which were reduced due to exposed to hypoglycemia. Overall, our results conclude that LiCl provides neuroprotection against hypoglycemia-induced apoptosis via activation of the canonical Wnt signaling pathway.

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