Irs2 deficiency alters hippocampus-associated behaviors during young adulthood

Biochem Biophys Res Commun. 2021 Jun 25:559:148-154. doi: 10.1016/j.bbrc.2021.04.101. Epub 2021 Apr 30.

Abstract

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and insulin resistance, has been recognized as a risk factor for cognitive impairment and dementia, including Alzheimer's disease (AD). Insulin receptor substrate2 (IRS2) is a major component of the insulin/insulin-like growth factor-1 signaling pathway. Irs2 deletion leads to life-threatening T2DM, promoting premature death in male mice regardless of their genetic background. Here, we showed for the first time that young adult male mice lacking Irs2 on a C57BL/6J genetic background (Irs2-/-/6J) survived in different experimental environments and displayed hippocampus-associated behavioral alterations. Young adult male Irs2-/-/6J mice also exhibit aberrant alterations in energy and nutrient sensors, such as AMP-activated protein kinase (AMPK) and glucose transporter3 (GLUT3), and reduced core body temperature accompanied by abnormal change in the temperature sensor in the brain. These results suggest that Irs2 deficiency-induced impairments of brain energy metabolism and thermoregulation contribute to hippocampus-associated behavioral changes in young adult male mice.

Keywords: AMPK; Behavior; GLUT3; Hippocampus; Insulin; Irs2; TRPV4; Type2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature Regulation
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism
  • Gene Deletion*
  • Hippocampus / metabolism*
  • Insulin Receptor Substrate Proteins / genetics*
  • Insulin Receptor Substrate Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • Insulin Receptor Substrate Proteins
  • Irs2 protein, mouse