Spatial and temporal pattern of purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

Abstract

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.

Impaired Hypercarbic and Hypoxic Responses from Developmental Loss of Cerebellar Purkinje Neurons: Implications for Sudden Infant Death Syndrome

“…Aside from species-related differences, Shaker mutant rats also differ from Lurcher mutants in both the temporal and spatial patterns of Purkinje cell loss. Shaker mutant rats comprise two groups, mild and strong, that differentially exhibit hereditary cerebellar Purkinje cell loss [47]. The mild Shaker group is characterized behaviorally by ataxic gait, and exhibits cerebellar Purkinje cell loss that occurs randomly, primarily in the anterior lobe, begins by PND 42 to 49, and culminates approximately by PND 90.…”

“…The “strong shaker” is characterized behaviorally by both ataxic gait and severe body tremors, and additionally exhibits near-complete cerebellar Purkinje cell loss in the anterior lobe that occurs by PND 90. Accompanying the early anterior lobe loss, Purkinje cells in the posterior lobe (lobules VIIb, VIII, IXa-c) continue to degenerate throughout the life of this model [45, 47]. …”

Compartmental organization of Purkinje cells in the mature and developing mouse cerebellum as revealed by an olfactory marker protein-lacZ transgene

“…Double labeling of afferent fiber and zebrin parasagittal compartments as well as zebrin and HNK-1 or P-path compartments indicates the existence of a persistent and complex PC heterogeneity. The on-off pattern of expression defined by the OMP-lacZ transgene along the mediolateral and anterior-posterior axes adds another level of complexity but contains numerous analogies to the patterns observed in several mutant mice, including meander tail (Hollander and Waggie, 1977), tottering (Hess and Wilson, 1991), swaying (Lane, 1967;Thomas et al, 1991), leaner (Herrup and Wilczynski, 1982), and the rat shaker mutant (Tolbert et al, 1995). In addition, a strong correspondence with parasagittal bands of OMP-lacZ expression (Fig.…”

Olivopontocerebellar Atrophy in Two Adult Cats, Sporadic Cases or New Genetic Entity

“…More complex primary cerebellar degenerations have been reported in dogs, including spinocerebellar degeneration, 15 and a multisystem degeneration involving the substantia nigra, caudate nuclei 12 which in some breeds exhibits a concurrent cerebral cortex degeneration. 9 Purkinje cell degeneration along a strictly organized spatial pattern has been reported in strong shaker mu-tant rats; 37 however, in these rats, the topography of Purkinje cell death was different, and the Purkinje cell decay did not lead to complete cerebellar cortex loss.…”