| First Author | Tanokashira D | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 559 |
| Pages | 148-154 | PubMed ID | 33940386 |
| Mgi Jnum | J:305564 | Mgi Id | MGI:6706014 |
| Doi | 10.1016/j.bbrc.2021.04.101 | Citation | Tanokashira D, et al. (2021) Irs2 deficiency alters hippocampus-associated behaviors during young adulthood. Biochem Biophys Res Commun 559:148-154 |
| abstractText | 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. |
