Harvey J, Shanley L J, O'Malley D, Irving A J
Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
Biochem Soc Trans. 2005 Nov;33(Pt 5):1029-32. doi: 10.1042/BST20051029.
It is well documented that the hormone leptin signals information regarding the status of fat stores to hypothalamic nuclei, which in turn control feeding behaviour and body weight. However, leptin and its receptor are widely expressed in many extra-hypothalamic brain regions, including hippocampus, brain stem and cerebellum. Moreover, evidence is accumulating that leptin has other neuronal functions that are unrelated to its effects on energy homeostasis. Indeed a role for leptin in neuronal development has been suggested as leptin-deficient rodents display abnormal brain development and leptin actively participates in the development of the hypothalamus. In the hippocampus, leptin is a potential cognitive enhancer as genetically obese rodents with dysfunctional leptin receptors display impairments in hippocampal synaptic plasticity. Moreover, direct administration of leptin into the hippocampus can facilitate hippocampal LTP (long-term potentiation) in vivo and improve memory processing in mice. At the cellular level, we have also shown that leptin has the capacity to convert short-term potentiation into LTP. Here, we review the data that leptin influences hippocampal synaptic plasticity via enhancing NMDA (N-methyl-D-aspartate) receptor function. We also provide evidence that rapid trafficking of NMDA receptors to the plasma membrane may underlie the effects of leptin on excitatory synaptic strength.
有充分的文献记载，激素瘦素会将有关脂肪储存状态的信息传递给下丘脑核，下丘脑核进而控制进食行为和体重。然而，瘦素及其受体在许多下丘脑外脑区广泛表达，包括海马体、脑干和小脑。此外，越来越多的证据表明，瘦素具有其他与能量稳态无关的神经元功能。事实上，由于瘦素缺乏的啮齿动物表现出异常的大脑发育，且瘦素积极参与下丘脑的发育，因此有人提出瘦素在神经元发育中发挥作用。在海马体中，瘦素是一种潜在的认知增强剂，因为瘦素受体功能失调的遗传性肥胖啮齿动物在海马体突触可塑性方面存在缺陷。此外，将瘦素直接注入海马体可在体内促进海马体的长时程增强（LTP），并改善小鼠的记忆处理能力。在细胞水平上，我们还表明瘦素具有将短期增强转化为LTP的能力。在此，我们综述了瘦素通过增强N-甲基-D-天冬氨酸（NMDA）受体功能来影响海马体突触可塑性的数据。我们还提供证据表明，NMDA受体向质膜的快速转运可能是瘦素对兴奋性突触强度产生影响的基础。
