Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse.

Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2) mouse (nax--naked-ataxia mutant mouse) correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc) degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR) plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5). In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.

Embryonic stages in cerebellar afferent development.

The cerebellum is important for motor control, cognition, and language processing. Afferent and efferent fibers are major components of cerebellar circuitry and impairment of these circuits causes severe cerebellar malfunction, such as ataxia. The cerebellum receives information from two major afferent types - climbing fibers and mossy fibers. In addition, a third set of afferents project to the cerebellum as neuromodulatory fibers. The spatiotemporal pattern of early cerebellar afferents that enter the developing embryonic cerebellum is not fully understood. In this review, we will discuss the cerebellar architecture and connectivity specifically related to afferents during development in different species. We will also consider the order of afferent fiber arrival into the developing cerebellum to establish neural connectivity.