Upregulation of Pin1 contributes to alleviation of cognitive dysfunction in diabetic mice

Brain Behav. 2023 Dec;13(12):e3336. doi: 10.1002/brb3.3336. Epub 2023 Nov 21.

Abstract

Objective: This study aimed to explore the molecular mechanism underlying the role of Pin1 in cognitive dysfunction in diabetic mice.

Methods: Using a streptozotocin-induced diabetic mouse model, an adeno-associated virus carrying the Pin1 gene was used to upregulate Pin1 expression in the hippocampus of diabetic mice. Animal behavior tests and molecular biology techniques were further used to explore the role of Pin1 in cognitive dysfunction in diabetic mice.

Results: Our study demonstrated that upregulation of Pin1 expression increased the phosphorylation of AKT and insulin receptor substrate 1 downstream signaling molecules of the IR-IGF1R pathway, increased the phosphorylation of GSK-3β, and concomitantly decreased the phosphorylation of Tau in the hippocampus of diabetic mice, thereby improving the ultrastructural pathology of the hippocampus and further alleviating diabetes-related cognitive impairment.

Conclusion: Pin1 can improve cognitive dysfunction in diabetic mice.

Keywords: Pin1; cognitive dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / metabolism
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hippocampus / metabolism
  • Mice
  • Phosphorylation
  • Signal Transduction
  • Up-Regulation

Substances

  • Glycogen Synthase Kinase 3 beta
  • Pin1 protein, mouse