Abstract
Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cognitive impairment. And the underlying mechanism remains unillustrated. HSPB8 is a member of the small heat shock protein family. In this study, we found that the expression of HSPB8 was upregulated in the hippocampus of high - fat diet (HFD) + streptozotocin (STZ) - induced diabetic mice and N2a cells exposed to high glucose. Overexpression of HSPB8 relieved cognitive decline in DM mice. Mechanically, HSPB8 overexpression in the hippocampus of diabetic mice inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation via dephosphorylating mitochondrial fission-associated protein dynamin-related protein 1 (DRP1) at the phosphorylated site Ser616 (p-Drp1S616). Furthermore, HSPB8 overexpression increased mitochondrial membrane potential (MMP) and reduced oxidative stress. These results indicate a protective effect of HSPB8 in the hippocampus of diabetic mice and N2a cells exposed to high glucose. Overexpression of HSPB8 might be a useful strategy for treating T2DM-related cognitive decline.