Irs2 deficiency alters hippocampus-associated behaviors during young adulthood

• Published in: Biochemical and biophysical research communications 2021-06, Vol.559, p.148-154
• Main Authors: Tanokashira, Daisuke, Wang, Wei, Maruyama, Megumi, Kuroiwa, Chiemi, White, Morris F., Taguchi, Akiko
• Format: Article
• Language: English
• Subjects: AMPK; Behavior; GLUT3; Hippocampus; Insulin; Irs2; TRPV4; Type2 diabetes
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.04.101

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. •Young adult male Irs2−/−/6J mice display hippocampus-associated behavioral changes.•Inactivation of Irs2 has aberrant effects on the brain energy metabolism in mice.•Irs2 deficiency-induced behavioral alterations are accompanied by thermoregulatory dysfunction.