Phosphorylated Glycogen Synthase Kinase-3β (GSK-3β) Improves Cognition in Rats with Diabetes-Associated Cognitive Decline

BACKGROUND The serine/threonine kinase glycogen synthase kinase-3ß (GSK-3ß) is involved in a broad range of cellular processes, including cell proliferation, apoptosis, and inflammation. GSK-3ß has been considered to play an important role in the pathogenesis of T2DM and AD, which is activated in both the periphery and central nervous system. However, the upstream and downstream factors and the underlying regulatory mechanisms of GSK-3ß in T2DM and AD are unclear. MATERIAL AND METHODS Here, we investigated the production of cytochrome C, Caspase-3, and Caspase-9 in in the hippocampus of DM rats and clarify the role of GSK-3ß in these processes. Streptozotocin (STZ)-induced DM rats presented increased GSK-3ß activity. RESULTS We found that cytochrome C, Caspase-3, and Caspase-9 were overproduced in the hippocampus. Furthermore, the cytochrome C, Caspase-3, and Caspase-9 levels were restored after GSK-3ß inhibitors Licl treatment. CONCLUSIONS Our results show that GSK-3ß regulates the production of cytochrome C, Caspase-3, and Caspase-9 in STZ-induced rat brain and may therefore contribute to DM-caused cognitive dysfunction via inhibition of neural cell apoptosis.