O'Malley Dervla, MacDonald Neil, Mizielinska Sarah, Connolly Christopher N, Irving Andrew J, Harvey Jenni
Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
Mol Cell Neurosci. 2007 Aug;35(4):559-72. doi: 10.1016/j.mcn.2007.05.001. Epub 2007 May 10.
Recent studies have implicated the hormone leptin in synaptic plasticity associated with neuronal development and learning and memory. Indeed, leptin facilitates hippocampal long-term potentiation and leptin-insensitive rodents display impaired hippocampal synaptic plasticity suggesting a role for endogenous leptin. Structural changes are also thought to underlie activity-dependent synaptic plasticity and this may be regulated by specific growth factors. As leptin is reported to have neurotrophic actions, we have examined the effects of leptin on the morphology and filopodial outgrowth in hippocampal neurons. Here, we demonstrate that leptin rapidly enhances the motility and density of dendritic filopodia and subsequently increases the density of hippocampal synapses. This process is dependent on the synaptic activation of NR2A-containing NMDA receptors and is mediated by the MAPK (ERK) signaling pathway. As dendritic morphogenesis is associated with activity-dependent changes in synaptic strength, the rapid structural remodeling of dendrites by leptin has important implications for its role in regulating hippocampal synaptic plasticity and neuronal development.
最近的研究表明，激素瘦素与神经元发育、学习和记忆相关的突触可塑性有关。事实上，瘦素促进海马体长期增强效应，而对瘦素不敏感的啮齿动物表现出海马体突触可塑性受损，这表明内源性瘦素发挥了作用。结构变化也被认为是活动依赖型突触可塑性的基础，这可能受特定生长因子调控。由于据报道瘦素有神经营养作用，我们研究了瘦素对海马神经元形态和丝状伪足生长的影响。在此，我们证明瘦素能迅速增强树突状丝状伪足的运动性和密度，随后增加海马体突触的密度。这一过程依赖于含NR2A的NMDA受体的突触激活，并由MAPK（ERK）信号通路介导。由于树突形态发生与突触强度的活动依赖型变化相关，瘦素对树突的快速结构重塑对其在调节海马体突触可塑性和神经元发育中的作用具有重要意义。
