Control of cortical neuronal migration by glutamate and GABA.
Control of cortical neuronal migration by glutamate and GABA.
复制标题
控制谷氨酸和GABA皮质神经元迁移。
DOI：
10.3389/fncel.2015.00004
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发表时间：
2015
影响因子：
5.3
通讯作者：
Kilb W
中科院分区：
文献类型：
--
作者：
Luhmann HJ;Fukuda A;Kilb W
神经元在大脑皮层的迁移受经典神经递质谷氨酸和GABA的旁分泌作用控制。谷氨酸主要通过作用于NMDA受体来控制锥体神经元的径向迁移，并通过激活非NMDA和NMDA受体来调节抑制性中间神经元的切向迁移。GABA作用于GABAA-Rho和GABAA受体，对径向迁移的神经元具有二分作用，在下层分别作为GO信号和在上皮质板(CP)作为停止信号。代谢性GABAB受体促进中间神经元向CP的径向迁移和切向迁移。除GABA外，内源性GABA能激动剂牛磺酸也是控制径向迁移的相关激动剂。在较小程度上，甘氨酸受体的激活也会影响径向和切向的迁移。谷氨酸和GABA受体的激活导致细胞内钙离子瞬变增加，这通过作用于细胞骨架促进神经元迁移。谷氨酸或GABA受体在皮质发生早期的药物或遗传操作会导致上层异位细胞团和皮质板层的丢失，即与神经或神经精神疾病相关的神经元迁移障碍。NMDA和离子型GABA受体在皮质神经元迁移中的关键作用具有重要的临床意义，因为作用于这些受体的一些药物(如抗癫痫药、麻醉药、酒精)在皮质新生的早期可能会干扰正常的迁移模式。
Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis.
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