Neuronal influence on glial enzyme expression: evidence from mutant mouse cerebella

Abstract The developmentally regulated enzyme sn-glycerol-3-phosphate dehydrogenase (GPDH; EC 1.1.1.8) is characteristically present in relatively high levels in mature Bergmann glia of the mouse cerebellum. Preliminary studies identified several neurological mouse mutants with reduced glial enzyme activity. Immunohistochemical examination of GPDH expression in three mutants (lurcher, nervous, and Purkinje cell degeneration) revealed a positive correlation between glial enzyme expression and Purkinje cell presence. Whereas GPDH immunoreactivity appears normal in Bergmann glia from all three mutants at early times, immunoreactivity diminishes fairly rapidly after Purkinje cell loss, first in the Bergmann glia somas and then in the processes. Loss of immunoreactivity is uniform throughout the cerebellar cortex in lurcher and Purkinje cell degeneration where the entire Purkinje cell populations die. In nervous mice, in which some Purkinje cells survive, GPDH immunoreactivity is patchy throughout the cortex; it is present only where Purkinje cells remain. In contrast, Bergmann fibers appear uniformly distributed throughout the cortex of mutant cerebella, as demonstrated by immunostaining for the presence of glial filaments. This observation suggest that the loss of GPDH immunoreactivity is not a result of glial cell death. These results support the idea that GPDH expression in Bergmann glia depends upon their sustained interaction with adjacent Purkinje cells.