Cholesterol-mediated neurite outgrowth is differently regulated between cortical and hippocampal neurons
Cholesterol-mediated neurite outgrowth is differently regulated between cortical and hippocampal neurons
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DOI：
10.1074/jbc.m509164200
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发表时间：
2005-12-30
影响因子：
4.8
通讯作者：
Michikawa, M
中科院分区：
文献类型：
--
作者：
Ko, M;Zou, K;Michikawa, M
神经元类型特异性形态发生的获得是神经元分化的中心特征，并且对区域特异性神经系统功能具有重要影响。在这里，我们报告说，细胞类型特异性胆固醇档案确定的差异调制的轴突和树突生长在海马和大脑皮层神经元的文化。皮层神经元轴突和树突的生长范围比海马神经元大，极性形成早。海马神经元的总匀浆和脂筏中胆固醇浓度显著高于皮层神经元。胆固醇消耗β-环糊精显着增强了神经突起的生长和加速建立海马神经元，这是类似的观察未处理的皮质神经元的神经元极性，而胆固醇负荷没有影响。相反，胆固醇的消耗和负荷都减少了皮质神经元的轴突生长。胆固醇消耗诱导的神经突生长和极性形成的刺激伴随着Fyn（一种Src激酶）在海马神经元脂筏中的定位增强。β-环糊精和Src家族激酶抑制剂PP 2的伴随治疗特异性阻断了海马神经元中的轴突生长，但不阻断树突生长（两者均通过β-环糊精增强），这表明胆固醇调节的轴突生长以Fyn依赖性方式诱导。这些结果表明，细胞胆固醇调节轴突和树突生长和神经元极化培养条件下，海马和皮质神经元之间的胆固醇分布的差异是这两种类型的神经元之间的轴突生长的差异的基础。
The acquisition of neuronal type-specific morphogenesis is a central feature of neuronal differentiation and has important consequences for region-specific nervous system functions. Here, we report that the cell type-specific cholesterol profile determines the differential modulation of axon and dendrite outgrowths in hippocampal and cerebral cortical neurons in culture. The extent of axon and dendrite outgrowths is greater and the polarity formation occurs earlier in cortical neurons than in hippocampal neurons. The cholesterol concentrations in total homogenate and the lipid rafts from hippocampal neurons are significantly higher than those from cortical neurons. Cholesterol depletion by beta-cyclodextrin markedly enhanced the neurite outgrowth and accelerated the establishment of neuronal polarity in hippocampal neurons, which were similarly observed in nontreated cortical neurons, whereas cholesterol loading had no effects. In contrast, both depletion and loading of cholesterol decreased the neurite outgrowths in cortical neurons. The stimulation of neurite outgrowth and polarity formation induced by cholesterol depletion was accompanied by an enhanced localization of Fyn, a Src kinase, in the lipid rafts of hippocampal neurons. A concomitant treatment with beta-cyclodextrin and a Src family kinase inhibitor, PP2, specifically blocked axon outgrowth but not dendrite outgrowth ( both of which were enhanced by beta-cyclodextrin) in hippocampal neurons, suggesting that axon outgrowth modulated by cholesterol is induced in a Fyn-dependent manner. These results suggest that cellular cholesterol modulates axon and dendrite outgrowths and neuronal polarization under culture conditions and also that the difference in cholesterol profile between hippocampal and cortical neurons underlies the difference in neurite outgrowth between these two types of neurons.