Expression of the alpha and beta subunits of Ca2+/calmodulin kinase II in the cerebellum of jaundiced Gunn rats during development: a quantitative light microscopic analysis

The homozygous (jj) jaundiced Gunn rat model for hyperbilirubinemia display s pronounced cerebellar hypoplasia. To examine the cellular mechanisms invo lved in bilirubin toxicity, this study focused on the effect of hyperbiliru binemia on calcium/calmodulin-dependent kinase LI (CaM kinase II). CaM kina se II is a neuronally enriched enzyme which performs several important func tions. Immunohistochemical analysis of alternating serial sections were per formed using monoclonal antibodies for the alpha and beta subunits of CaM k inase II. Measurements were made of the total numbers of stained cells in e ach of the deep cerebellar nuclei and of Purkinje and granule cell densitie s in cerebellar lobules II, VI, and IX. The beta subunit was present in Pur kinje cells and deep cerebellar nuclei of both groups at all ages, but only granule cells which had migrated through the Purkinje cell layer showed st aining for beta subunit; external granule cells were completely negative. M any Purkinje cells had degenerated in the older animals, and the percent of granule cells stained for beta subunit was significantly reduced. The a su bunit was found exclusively in Purkinje cells, although its appearance was delayed in the jaundiced animals. Sulfadimethoxine was administered to some jj rats 24 h or 15 days prior to sacrifice to increase brain bilirubin con centration. Results showed that bilirubin exposure modulated both alpha and beta CaM kinase II subunit expression in selective neuronal populations, b ut sulfadimethoxine had no acute effect on enzyme immunoreactivity. Thus, d evelopmental expression of the alpha and beta subunits of CaM Iiinase II wa s affected by chronic bilirubin exposure during early postnatal development of jaundiced Gunn rats.