Immunohistochemical studies of GABA and parvalbumin in the developing human cerebellum

The localization of GABA and parvalbumin was studied in the developing cerebellum of human fetuses from 16 to 28 weeks of gestation. The avidin-biotin complex immunohistochemical method combined with silver staining were used to reveal the presence of GABA- and parvalbumin-positive neurons and nerve fibres. As early as the 16th week of gestation, GABA immunopositivity was observed in the cerebellar cortex and the deep nuclei. GABA-positive neurons included Purkinje cells, stellate and basket cells of the cerebellar cortex and neurons in the deep nuclei. The gradient of immunoreactivity increased with the maturing cells, being weak at 16 weeks and becoming markedly pronounced at 28 weeks of gestation. GABA-immunopositive mossy fibres were observed in the granular cell layer at 16 weeks, and by 28 weeks, a robust fibre network was present in the cortex and deep nuclei. Immunohistochemical localization for parvalbumin indicates that weak immunoreactivity was observed in Purkinje cells, stellate and basket cells at 16 weeks of gestation, increasing in intensity with advancing age, notably in the Purkinje cells which had acquired an elaborate arbor of neurites at 28 weeks of gestation. In the deep nuclei, parvalbumin-positive cells and nerve fibres were observed throughout the 16 to 28 week period. These results indicate that GABA- and parvalbumin-positive neurons and fibres appeared as early as 16 weeks of gestation, expressing a high degree of immunoreactivity by the 28 week of fetal age.