Galas Ludovic, Bénard Magalie, Lebon Alexis, Komuro Yutaro, Schapman Damien, Vaudry Hubert, Vaudry David, Komuro Hitoshi
Normandie University, UNIROUEN, INSERM, Regional Cell Imaging Platform of Normandy (PRIMACEN), 76000 Rouen, France.
Department of Neurophysiology, Donders Centre for Neuroscience, Radboud University, Nijmegen 6525 AJ, The Netherlands.
Brain Sci. 2017 Jun 6;7(6):62. doi: 10.3390/brainsci7060062.
Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders.
由于小脑在出生后仍持续发育,它成为研究中间神经元迁移的出生后编排的独特模型。荧光标记与体内/体外成像相结合,揭示了小脑皮质层(外颗粒层、分子层、浦肯野细胞层和内颗粒层)内的细胞高速公路网络。在出生后的前两周,跳跃运动、短暂的停顿阶段、细胞间相互作用/接触以及细胞外基质的降解勾勒出小脑中间神经元,尤其是颗粒细胞和篮状/星状细胞到达其最终位置的路线。此外,已表明皮质层特异性调节因子,如神经肽(垂体腺苷酸环化酶激活多肽(PACAP)、生长抑素)或蛋白质(组织型纤溶酶原激活剂(tPA)、胰岛素生长因子-1(IGF-1))可抑制或刺激中间神经元的迁移过程。这些因子表现出进一步的复杂性,因为生长抑素、PACAP或tPA对中间神经元迁移的影响取决于它们作用于哪一层或哪种细胞类型,可能产生相反的作用或没有影响。源自环境条件(光刺激、污染物)、营养物质或滥用药物(酒精)的外部因素也会改变正常的细胞迁移,导致小脑疾病。