Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity

• Metformin pretreatment protects CGNs against glutamate neuronal toxicity.
• Metformin reduces glutamate-induced Caspase 3 activation.
• Glutamate-induced JNK and p38 phosphorylation are inhibited by metformin.

Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders.