Cell death and neurodegeneration in the postnatal development of cerebellar vermis in normal and Reeler mice

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• 作者：Claudia Castagna ; ^{claudia.castagna@unito.it" class="auth_mail" title="E-mail the corresponding author} ; Adalberto Merighi ; Laura Lossi
• 关键词：Cerebellum ; Apoptosis ; Autophagy ; Ultrastructure ; Granule cells ; Mouse ; Development
• 刊名：Annals of Anatomy - Anatomischer Anzeiger
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：207
• 期：Complete
• 页码：76-90
• 全文大小：5870 K

文摘

Programmed cell death (PCD) was demonstrated in neurons and glia in normal brain development, plasticity, and aging, but also in neurodegeneration. (Macro)autophagy, characterized by cytoplasmic vacuolization and activation of lysosomal hydrolases, and apoptosis, typically entailing cell shrinkage, chromatin and nuclear condensation, are the two more common forms of PCD. Their underlying intracellular pathways are partly shared and neurons can die following both modalities, according to the type of death-triggering stimulus.

Reelin is an extracellular protein necessary for proper neuronal migration and brain lamination. In the mutant Reeler mouse, its absence causes neuronal mispositioning, with a notable degree of cerebellar hypoplasia that was tentatively related to an increase in PCD. We have carried out an ultrastructural analysis on the occurrence and type of postnatal PCD affecting the cerebellar neurons in normal and Reeler mice. In the forming cerebellar cortex, PCD took the form of apoptosis or autophagy and mainly affected the cerebellar granule cells (CGCs). Densities of apoptotic CGCs were comparable in both mouse strains at P0-P10, while, in mutants, they increased to become significantly higher at P15. In WT mice the density of autophagic neurons did not display statistically significant differences in the time interval examined in this study, whereas it was reduced in Reeler in the P0-P10 interval, but increased at P15. Besides CGCs, the Purkinje neurons also displayed autophagic features in both WT and Reeler mice. Therefore, cerebellar neurons undergo different types of PCD and a Reelin deficiency affects the type and degree of neuronal death during postnatal development of the cerebellum.