Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
Eur J Neurosci. 2013 May;37(9):1369-82. doi: 10.1111/ejn.12152. Epub 2013 Feb 6.
Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time-lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell-derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron-like cells emerging from the neurosphere and increased motility of neuron-like cells. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron-like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.
神经递质，如谷氨酸，是神经发生的潜在调节物。干扰特定的谷氨酸受体亚型会影响神经祖细胞的增殖、迁移和分化。不同谷氨酸受体配体作用的细胞靶点知之甚少。在这项研究中，我们结合钙成像、膜电位测量、延时成像和免疫细胞化学，获得了对谷氨酸受体激动剂和拮抗剂反应的迁移的小鼠胚胎神经祖细胞衍生细胞的空间概述。通过代谢型谷氨酸受体 5 的反应与放射状胶质细胞相关联，并且在靠近神经球的内迁移区占主导地位。代谢型谷氨酸受体 5 的阻断导致放射状胶质细胞过程变短，从神经球中出现的神经元样细胞短暂增加，以及神经元样细胞的迁移增加。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/海人藻酸受体存在于大多数迁移的神经元细胞上，这些细胞随着时间的推移积累在迁移区的外边缘。阻断这些受体导致放射状胶质细胞过程的延伸增强和神经元样细胞的迁移减少。我们的结果表明，功能性谷氨酸受体对神经祖细胞的迁移有深远的影响。代谢型谷氨酸受体 5 的主要靶标似乎是放射状胶质细胞，而 AMPA/海人藻酸受体主要表达在新生神经元细胞中，并调节这些细胞的迁移进展。结果表明，代谢型谷氨酸受体 5 和 AMPA/海人藻酸受体都对迁移的胚胎祖细胞的导向很重要。
