Gundelach Jannis, Koch Michael
Department of Neuropharmacology, Center for Cognitive Sciences, University of Bremen, Bremen, Germany.
Neural Regen Res. 2020 Sep;15(9):1740-1747. doi: 10.4103/1673-5374.276335.
The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee (522-27-11/02-00, 115; Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.
神经细胞黏附分子的结合特性受多唾液酸部分的调节。这在成年新生神经母细胞从其起源区域即脑室下区向嗅球的迁移中起重要作用。多唾液酸化增加了细胞的迁移速度，并有助于防止神经母细胞离开其迁移路径——嘴侧迁移流。在此，我们在大鼠前额叶皮质结构损伤模型中评估了脑室内应用神经氨酸酶-N（一种能特异性从神经细胞黏附分子上切割多唾液酸的酶）的潜力。正如预期的那样，神经氨酸酶-N使嘴侧迁移流变宽，细胞取向的均匀性降低。此外，神经氨酸酶-N处理导致神经母细胞离开嘴侧迁移流并向损伤组织迁移。尽管在三周的存活期后神经母细胞未分化为神经元，但该技术为未来关于重新定位的神经母细胞迁移和分化的研究提供了一个可靠的动物模型，并且可能为未来基于内源性干细胞的脑结构损伤治疗提供基础。这些实验于2016年2月10日获得当地动物护理委员会（522 - 27 - 11/02 - 00, 115；德国不来梅科学、健康与消费者保护参议员）的批准。
