Differential glial activation during the degeneration of Purkinje cells and mitral cells in the PCD mutant mice

Abstract

[EN]Purkinje Cell Degeneration (PCD) mice harbor a nna1 genemutation which leads to an early and rapid degeneration ofPurkinje cells (PC) between the third and fourth week ofage. This mutation also underlies the death of mitral cells(MC) in the olfactory bulb (OB), but this process is slowerand longer than in PC. No clear interpretations supportingthe marked differences in these neurodegenerative proc-esses exist. Growing evidence suggests that either benefi-cial or detrimental effects of gliosis in damaged regionswould underlie these divergences. Here, we examined thegliosis occurring during PC and MC death in the PCDmouse. Our results demonstrated different glial reactionsin both affected regions. PC disappearance stimulated asevere gliosis characterized by strong morphologicalchanges, enhanced glial proliferation, as well as the releaseof pro-inflammatory mediators. By contrast, MC degenera-tion seems to promote a more attenuated glial response inthe PCD OB compared with that of the cerebellum. Strik-ingly, cerebellar oligodendrocytes died by apoptosis in thePCD, whereas bulbar ones were not affected. Interestingly,the level of nna1 mRNA under normal conditions washigher in the cerebellum than in the OB, probably relatedto a faster neurodegeneration and stronger glial reaction inits absence. The glial responses may thus influence theneurodegenerative course in the cerebellum and OB of themutant mouse brain, providing harmful and beneficialmicroenvironments, respectively