Case Sami L, Frazier Hilaree N, Anderson Katie L, Lin Ruei-Lung, Thibault Olivier
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, 780 Rose Street, Lexington, KY 40536, USA.
Biomedicines. 2022 Aug 9;10(8):1923. doi: 10.3390/biomedicines10081923.
Insulin resistance, which manifests as a reduction of insulin receptor signaling, is known to correlate with pathological changes in peripheral tissues as well as in the brain. Central insulin resistance has been associated with impaired cognitive performance, decreased neuronal health, and reduced brain metabolism; however, the mechanisms underlying central insulin resistance and its impact on brain regions outside of those associated with cognition remain unclear. Falls are a leading cause of both fatal and non-fatal injuries in the older population. Despite this, there is a paucity of work focused on age-dependent alterations in brain regions associated with ambulatory control or potential therapeutic approaches to target these processes. Here, we discuss age-dependent alterations in central modalities that may contribute to gait dysregulation, summarize current data supporting the role of insulin signaling in the brain, and highlight key findings that suggest insulin receptor sensitivity may be preserved in the aged brain. Finally, we present novel results showing that administration of insulin to the somatosensory cortex of aged animals can alter neuronal communication, cerebral blood flow, and the motivation to ambulate, emphasizing the need for further investigations of intranasal insulin as a clinical management strategy in the older population.
胰岛素抵抗表现为胰岛素受体信号传导减少，已知与外周组织以及大脑的病理变化相关。中枢胰岛素抵抗与认知功能受损、神经元健康下降和脑代谢降低有关；然而，中枢胰岛素抵抗的潜在机制及其对与认知无关的脑区的影响仍不清楚。跌倒是老年人群致命和非致命伤害的主要原因。尽管如此，针对与动态控制相关的脑区中与年龄相关的变化或针对这些过程的潜在治疗方法的研究工作却很少。在此，我们讨论可能导致步态失调的中枢模式中与年龄相关的变化，总结支持胰岛素信号在大脑中作用的当前数据，并强调表明老年大脑中胰岛素受体敏感性可能得以保留的关键发现。最后，我们展示了新的结果，即向老年动物的体感皮层注射胰岛素可改变神经元通讯、脑血流量和行走动机，强调了进一步研究鼻内胰岛素作为老年人群临床管理策略的必要性。
