Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom.
Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom.
Neuropharmacology. 2018 Jul 1;136(Pt B):298-306. doi: 10.1016/j.neuropharm.2017.09.038. Epub 2017 Oct 5.
Accumulating evidence indicates that diet and body weight are important factors associated with Alzheimer's disease (AD), with a significant increase in AD risk linked to mid-life obesity, and weight loss frequently occurring in the early stages of AD. This has fuelled interest in the hormone leptin, as it is an important hypothalamic regulator of food intake and body weight, but leptin also markedly influences the functioning of the hippocampus; a key brain region that degenerates in AD. Increasing evidence indicates that leptin has cognitive enhancing properties as it facilitates the cellular events that underlie hippocampal-dependent learning and memory. However, significant reductions in leptin's capacity to regulate hippocampal synaptic function occurs with age and dysfunctions in the leptin system are associated with an increased risk of AD. Moreover, leptin is a potential novel target in AD as leptin treatment has beneficial effects in various models of AD. Here we summarise recent advances in leptin neurobiology with particular focus on regulation of hippocampal synaptic function by leptin and the implications of this for neurodegenerative disorders like AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
越来越多的证据表明，饮食和体重是与阿尔茨海默病（AD）相关的重要因素，中年肥胖会显著增加 AD 风险，而 AD 早期常出现体重下降。这激发了人们对激素瘦素的兴趣，因为它是调节食物摄入和体重的重要下丘脑激素，但瘦素也显著影响海马体的功能；海马体是 AD 中退化的关键大脑区域。越来越多的证据表明，瘦素有增强认知的特性，因为它促进了海马体依赖学习和记忆的细胞事件。然而，随着年龄的增长，瘦素调节海马突触功能的能力显著下降，瘦素系统功能障碍与 AD 风险增加有关。此外，瘦素是 AD 的一个潜在的新靶点，因为瘦素治疗在各种 AD 模型中都有有益的效果。本文总结了瘦素神经生物学的最新进展，特别关注瘦素对海马突触功能的调节及其对 AD 等神经退行性疾病的影响。本文是题为“代谢障碍作为神经退行性疾病风险因素”的特刊的一部分。
