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

Maryam Rahimi Balaei,Xiaodan Jiao,Pegah Afsharinezhad,Hassan Marzban,Niloufar Ashtari,Saeid Ghavami

doi:10.3390/ijms17010115

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

Maryam Rahimi Balaei, Xiaodan Jiao + Show 4 more

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https://doi.org/10.3390/ijms17010115

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Abstract

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.

Highlights

Lysosomal acid phosphatase 2 (Acp2) is a key enzyme in cerebellar development [1,2,3], and it is implicated in a variety of neurological disorders including progressive supranuclear palsy [4] and juvenile neuronal ceroid lipofuscinosis, known as Batten disease (a disease induced by mutations in the lysosomal protein ceroid-lipofuscinosis neuronal 3 (CLN3)) [5]
According to differential gene expressions, the cerebellum has been divided into four transverse zones including: (1) the anterior zone (AZ: lobules I–V); (2) the central zone (CZ: lobules VI–VII: with two sub-zones—see [8,9]); (3) the posterior zone (PZ: lobules VIII + dorsal lobule IX); and (4) the nodular zone (NZ: ventral lobule IX + lobule X) (e.g., [1,10,11])
We investigated p75 neurotrophin receptor (p75NTR) pattern and protein expression in the nax mouse with severe cerebellar anomalies and Purkinje cell (Pc) degeneration and in the wt sibling cerebellum

Summary

Introduction

Lysosomal acid phosphatase 2 (Acp2) is a key enzyme in cerebellar development [1,2,3], and it is implicated in a variety of neurological disorders including progressive supranuclear palsy [4] and juvenile neuronal ceroid lipofuscinosis, known as Batten disease (a disease induced by mutations in the lysosomal protein ceroid-lipofuscinosis neuronal 3 (CLN3)) [5]. Mounting evidence indicates that a spontaneous autosomal recessive mutation in Acp is responsible for occurrence of a neurocutaneous disorder that is correlated with abnormal skin and cerebellar development, and is called naked-ataxia (nax) mice [2,3]. In addition to the nax mouse, several studies have used the Acp transgenic animal model to investigate the role of Acp deficiency in development of the nervous system, in the cerebellum [2,3,6,7]. Much of the cerebellar patterning seems to have been built on the Purkinje cell (Pc) scaffold [13] because cerebellar cell types, functions and their afferent and efferent roles are aligned in a zone and stripe pattern [14,15,16]

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