| First Author | Song J | Year | 2015 |
| Journal | Neuroscience | Volume | 301 |
| Pages | 26-38 | PubMed ID | 26047734 |
| Mgi Jnum | J:225357 | Mgi Id | MGI:5693179 |
| Doi | 10.1016/j.neuroscience.2015.05.072 | Citation | Song J, et al. (2015) Impairment of insulin receptor substrate 1 signaling by insulin resistance inhibits neurite outgrowth and aggravates neuronal cell death. Neuroscience 301:26-38 |
| abstractText | In the central nervous system (CNS), insulin resistance (I/R) can cause defective neurite outgrowth and neuronal cell death, which can eventually lead to cognitive deficits. Recent research has focused on the relationship between I/R and the cognitive impairment caused by dementia, with the goal of developing treatments for dementia. Insulin signal transduction mediated by insulin receptor substrate (IRS-1) has been thoroughly studied in the CNS of patients with I/R. In the present study, we investigated whether the impairment of IRS-1-mediated insulin signaling contributes to neurite outgrowth and neuronal loss, both in mice fed a high-fat diet and in mouse neuroblastoma (Neuro2A) cells. To investigate the changes caused by the inhibition of IRS-1-mediated insulin signaling in the brain, we performed Cresyl Violet staining and immunochemical analysis. To investigate the changes caused by the inhibition of IRS-1-mediated insulin signaling in neuroblastoma cells, we performed Western blot analysis, reverse transcription-PCR, and immunochemical analysis. We show that the deactivation of IRS-1-mediated insulin signaling can inhibit neuronal outgrowth and aggravate neuronal cell death in the insulin-resistant CNS. Thus, IRS-1-mediated insulin signal transduction may be an important factor in the treatment of cognitive decline induced by I/R. |
