Calbindin immunoreactivity in the developing and adult human cerebellum

Abstract

Calbindin (CALB), a calcium-binding protein, is known to be expressed in the embryonic nervous system. In this study, we have examined its distribution in the cerebellum of human fetuses (11-25 weeks of gestation) and adult by immunohistochemistry. At the gestational age of 11-12 weeks, CALB immunoreactivity was present in granule and Purkinje cells throughout the cerebellum. By 16-21 weeks of gestation, immunoreactive Purkinje cells were well-differentiated in the vermis and flocculus, and their axons ran towards the deep cerebellar nuclei area, while the axon collaterals were seen to be distributed into adjacent folia. At the gestational period of 24-25 weeks, most Purkinje cells of the flocculus and vermis were arranged in one to two rows, while those of the hemispheres were still undifferentiated. A few Golgi cells of the vermis showed immunoreactivity. The neurons of the deep nuclei were immunonegative right from the gestational age of 11 weeks although a fine stippled staining of fibers was present throughout the body of all nuclei. The fibers lying close to the hilum of the dentate nucleus were strongly CALB-positive. The vestibulocerebellar fibers, being traced at the level of lower pons and upper medulla oblongata were stained as early as 11 weeks of gestation, whereas the olivocerebellar fibers were stained from 16 weeks onward. In the adult cerebellum, Purkinje cells were moderately immunopositive while granule cells were faintly stained; no other cells, including those of the deep nuclei were stained. In the medulla oblongata, the inferior olivary nucleus and olivocerebellar fibers were strongly CALB-positive. Our results indicate that CALB is expressed in early migratory Purkinje cells, and their maturation occurs in a vermal-to-hemisphere gradient. It is likely that CALB plays a significant role in the regulation of Ca²⁺-dependent activities in the developing cerebellum.