Podkletnova I, Rothstein J D, Helén P, Alho H
University of Tampere, Medical School, PO Box 607, 33101, Tampere, Finland.
Int J Dev Neurosci. 2001 Feb;19(1):47-52. doi: 10.1016/s0736-5748(00)00069-1.
Depletion of noradrenaline in newborn rats by 6-hydroxydopamine (6-OHDA) affects the postnatal development and reduces the granular cell area in the neocerebellum (lobules V-VII). During the first postnatal month, Bergmann glial fibers guide the migration of immature granule cells to the internal granule cell layer. Microglia and Bergmann glia may play an important role in this process, but the exact mechanism behind this phenomenon is not known. We studied the effect of systemic administration of 6-OHDA on the expression and localization on microglia and Bergmann glia in the neonatal cerebellum by immunohistochemistry. In the neocerebellum, 6-OHDA treatment caused a significant increase in the number of activated microglia. The increase was observed mainly in the granule cell layer and the cerebellar medulla. Bergmann glial cells in treated brains were abnormally located, did not form intimate associations with Purkinje cells, and the glial fibers were structurally different. Our findings indicate that a noradrenergic influence may be necessary for the normal maturation and migration of granule cells, and abnormal migration may be the result of Bergmann glia destruction and the activation of microglia. Activated microglia in the granule cell layer may be used as a marker for an injured cerebellar area.
用6-羟基多巴胺（6-OHDA）耗尽新生大鼠体内的去甲肾上腺素会影响产后发育，并减少新小脑（小叶V-VII）中的颗粒细胞区域。在出生后的第一个月，伯格曼胶质纤维引导未成熟颗粒细胞迁移至内颗粒细胞层。小胶质细胞和伯格曼胶质细胞可能在此过程中起重要作用，但这一现象背后的确切机制尚不清楚。我们通过免疫组织化学研究了全身注射6-OHDA对新生小鼠小脑中的小胶质细胞和伯格曼胶质细胞的表达及定位的影响。在新小脑中，6-OHDA处理导致活化小胶质细胞数量显著增加。这种增加主要出现在颗粒细胞层和小脑髓质。经处理的大脑中的伯格曼胶质细胞位置异常，与浦肯野细胞未形成紧密联系，且胶质纤维结构不同。我们的研究结果表明，去甲肾上腺素能影响可能是颗粒细胞正常成熟和迁移所必需的，异常迁移可能是伯格曼胶质细胞破坏和小胶质细胞活化的结果。颗粒细胞层中活化的小胶质细胞可用作小脑损伤区域的标志物。
