Heat shock protein 25 expression and preferential Purkinje cell survival in the <i>lurcher</i> mutant mouse cerebellum

Abstract

The spatial organization of the mouse cerebellum into transverse zones and parasagittal stripes is reflected during the temporal progression of Purkinje cell death in the Lurcher mutant mouse (+/Lc). Neurodegeneration in the +/Lc mutant is apparent by the second postnatal week and is initially seen in all four transverse zones: the anterior (lobules I-V), central (lobules VI, VII), posterior (lobules VIII, dorsal IX), and nodular (ventral lobule IX and lobule X) zone. However, from postnatal day (P)25-P36, Purkinje cell loss proceeds more rapidly in the anterior zone, followed by the posterior and central zones, and is significantly delayed in the nodular zone. Coronal sections through the +/Lc cerebellum reveal that surviving Purkinje cells are restricted to the paraflocculus/flocculus and the nodular zone and could be detected as late as P146 (approximately 5 months). Within this region, the pattern of preferentially surviving calbindin-immunoreactive Purkinje cells reflects the expression of the constitutively expressed small heat shock protein HSP25 in the wild-type cerebellum. Although the role of constitutively expressed HSP25 in the wild-type cerebellum is not clear, it appears to play a neuroprotective role in the flocculonodular region of the +/Lc mutant cerebellum as the percentage of surviving Purkinje cells that are HSP25-immunopositive significantly increases over time.