Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency
Abnormal cerebellar histogenesis in PEX2 Zellweger mice reflects multiple neuronal defects induced by peroxisome deficiency
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DOI：
10.1002/cne.10699
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发表时间：
2003-06-30
影响因子：
2.5
通讯作者：
Faust, PL
中科院分区：
文献类型：
--
作者：
Faust, PL
小脑的形式和回路是通过一个复杂的过程发展的，该过程需要整合多个神经元群体之间的传入-目标相互作用以及神经元-胶质细胞相互作用建立的迁移模式。对缺乏 PEX2 过氧化物酶体组装基因（其中过氧化物酶体功能被破坏）的小鼠进行的分析揭示了由于神经元内多个细胞过程的紊乱而导致的小脑组织发生异常。小脑生长和头尾叶状结构的缺陷反映了颗粒神经元数量的减少和浦肯野细胞树突发育的异常。在颗粒神经元中，凋亡细胞死亡增加，并且从 EGL 到 IGL 的运动延迟，这反映了细胞周期、成熟和迁移异常。底层的浦肯野细胞具有发育不良的树突乔木，具有异常的分支模式，这可能反映了延迟的颗粒神经元易位引起的诱导影响的改变。突变体橄榄攀缘纤维的延迟分枝及其从浦肯野细胞的体周到树突区室的缺陷易位导致浦肯野细胞的体细胞和近端树突上出现许多刺。远端浦肯野细胞树突棘也表现出异常的形态。这些浦肯野细胞树突异常与持续且增大的轴突球体相关，进一步表明浦肯野细胞内存在退行性过程。这种用于人类过氧化物酶体生物发生障碍 Zellweger 综合征的 PEX2(-/-) 小鼠模型说明了小脑异常发育过程的复杂相互作用以及过氧化物酶体功能对神经元迁移、增殖、分化和存活的重要性。 (C) 2003 Wiley-Liss, Inc.
The form and circuitry of the cerebellum develops by a complex process that requires integration of afferent-target interactions between multiple neuronal populations and migratory patterns established by neuron-glial interactions. Analysis of mice lacking the PEX2 peroxisome assembly gene, in which peroxisomal function is disrupted, reveals abnormal cerebellar histogenesis due to the disturbance of multiple cellular processes within neurons. Defects in cerebellar growth and the rostro-caudal foliation pattern reflect a reduced granule neuron population and abnormal Purkinje cell dendrite development. In granule neurons, there is increased apoptotic cell death and delayed movement from the EGL to IGL that reflects cell cycle, maturational and migrational abnormalities. The underlying Purkinje cells have stunted dendrite arbors with abnormal branching patterns, which may reflect altered inductive influences from the delayed granule neuron translocation. A delayed arborization of mutant olivary climbing fibers and their defective translocation from the perisomatic to the dendritic compartment of Purkinje cells results in numerous spines on the soma and proximal dendrites of Purkinje cells. Distal Purkinje cell dendritic spines also display abnormal morphology. These Purkinje cell dendritic abnormalities are seen in association with persistent and enlarged axonal spheroids, further indicating the presence of a degenerative process within the Purkinje cell. This PEX2(-/-) mouse model for the human peroxisomal biogenesis disorder Zellweger syndrome illustrates the complex interplay of abnormal developmental processes in the cerebellum and the importance of peroxisomal function for neuronal migration, proliferation, differentiation, and survival. (C) 2003 Wiley-Liss, Inc.