Patterned cell death in the lurcher mutant mouse cerebellum
The Lurcher mutant mouse (+/'Lc') is a widely studied model of excitotoxic Purkinje cell degeneration in the cerebellum. This study demonstrates that the spatial organization of the wildtype mouse cerebellum into transverse zones and parasagittal stripes is reflected during the temporal progression of Purkinje cell death in the +/'Lc'. Initially, neurodegeneration in the +/'Lc' is 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. From postnatal days (P)25-P36, Purkinje cell survival is restricted to the nodular zone, including the paraflocculus/flocculus, and was detected as late as Pl46 (~5 months). Surviving Purkinje cells express heat shock protein (HSP) 25 suggesting it may playa neuroprotective role in the flocculonodular region of the +/'Lc'. HSP25, HSP70, HSP90 and somatostatin28 are progressively upregulated in the +/'Lc' cerebellum, possibly providing support and repair during neurodegeneration.