Division of Systems Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
Division of Systems Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
Vitam Horm. 2021;115:105-127. doi: 10.1016/bs.vh.2020.12.006. Epub 2021 Jan 30.
It is widely accepted that the metabolic hormone leptin regulates food intake and body weight via activation of hypothalamic leptin receptors. However, as leptin receptors are also highly expressed in other brain regions, such as the hippocampus, alterations in leptin responsiveness also impacts on key functions of the hippocampus, like learning and memory. Within the hippocampus, high levels of leptin receptors are expressed at excitatory synapses, and in accordance with a synaptic localization, leptin potently regulates synaptic transmission at both Schaffer collateral (SC) and temporoammonic (TA) inputs to CA1 pyramidal neurons. Increasing evidence from cellular and behavioral studies examining leptin action at CA1 synapses support the notion that leptin is a potential cognitive enhancer. However, the capacity of leptin to regulate synaptic efficacy at SC-CA1 and TA-CA1 synapses declines in an age-dependent manner. Moreover, clinical evidence that supports a link between circulating leptin levels and the risk of the age-related neurodegenerative disorder, Alzheimer's disease (AD) is accumulating. Consequently, it has been proposed that the leptin system is a potential therapeutic target in AD, and that boosting the hippocampal actions of leptin may be beneficial in the treatment of AD. Here we review recent progress in our understanding of the neuronal and hippocampal synaptic functions that are regulated by leptin and how alterations in the leptin system influence age-related CNS-related disorders like AD.
人们普遍认为代谢激素瘦素通过激活下丘脑瘦素受体来调节食物摄入和体重。然而，由于瘦素受体也在大脑的其他区域（如海马体）高度表达，瘦素反应的改变也会影响海马体的关键功能，如学习和记忆。在海马体中，高水平的瘦素受体表达在兴奋性突触上，并且根据突触定位，瘦素强烈调节 CA1 锥体神经元的 Schaffer 侧枝（SC）和颞侧（TA）传入的突触传递。越来越多的细胞和行为研究证据表明，瘦素在 CA1 突触上的作用支持了瘦素是一种潜在的认知增强剂的观点。然而，瘦素调节 SC-CA1 和 TA-CA1 突触效能的能力会随着年龄的增长而下降。此外，越来越多的临床证据表明，循环瘦素水平与年龄相关的神经退行性疾病阿尔茨海默病（AD）的风险之间存在关联。因此，有人提出瘦素系统是 AD 的一个潜在治疗靶点，增强瘦素对海马体的作用可能有益于 AD 的治疗。在这里，我们回顾了最近在理解瘦素调节的神经元和海马体突触功能方面的进展，以及瘦素系统的改变如何影响 AD 等与年龄相关的中枢神经系统疾病。
