School of Biomolecular and Biomedical Science, The Conway Institute, University College Dublin, Dublin, Ireland.
Division of Systems Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom.
Prog Lipid Res. 2021 Apr;82:101098. doi: 10.1016/j.plipres.2021.101098. Epub 2021 Apr 22.
Significant advances have been made in our understanding of the hormone, leptin and its CNS actions in recent years. It is now evident that leptin has a multitude of brain functions, that extend beyond its established role in the hypothalamic control of energy balance. Additional brain regions including the hippocampus are important targets for leptin, with a high density of leptin receptors (LepRs) expressed in specific hippocampal regions and localised to CA1 synapses. Extensive evidence indicates that leptin has pro-cognitive actions, as it rapidly modifies synaptic efficacy at excitatory Schaffer collateral (SC)-CA1 and temporoammonic (TA)-CA1 synapses and enhances performance in hippocampal-dependent memory tasks. There is a functional decline in hippocampal responsiveness to leptin with age, with significant reductions in the modulatory effects of leptin at SC-CA1 and TA-CA1 synapses in aged, compared to adult hippocampus. As leptin has pro-cognitive effects, this decline in leptin sensitivity is likely to have negative consequences for cognitive function during the aging process. Here we review how evaluation of the hippocampal actions of leptin has improved our knowledge of the regulatory brain functions of leptin in health and provided significant insight into the impact of leptin in age-related neurodegenerative disorders linked to cognitive decline.
近年来，我们对激素瘦素及其在中枢神经系统中的作用有了重要的认识。现在已经很明显，瘦素具有多种脑功能，超出了其在下丘脑对能量平衡控制中的既定作用。包括海马体在内的其他脑区也是瘦素的重要靶点，特定海马区域表达有高密度的瘦素受体 (LepR)，并定位于 CA1 突触。大量证据表明瘦素有促进认知的作用，因为它可以迅速改变兴奋性 Schaffer 侧枝 (SC)-CA1 和颞侧弓状核 (TA)-CA1 突触的突触效能，并增强海马依赖记忆任务的表现。随着年龄的增长，海马体对瘦素的反应能力会下降，与成年海马体相比，老年海马体中瘦素对 SC-CA1 和 TA-CA1 突触的调节作用显著降低。由于瘦素有促进认知的作用，瘦素敏感性的这种下降可能会对衰老过程中的认知功能产生负面影响。在这里，我们回顾了瘦素对海马体作用的评估如何提高了我们对瘦素在健康状态下调节大脑功能的认识，并深入了解了瘦素在与认知能力下降相关的年龄相关性神经退行性疾病中的作用。
