Immunohistochemical analysis of developmental stage of external granular layer neurons which undergo apoptosis in postnatal rat cerebellum.

Some granule neurons naturally undergo apoptosis in the external granular layer (EGL) of the postnatally developing rat cerebellum. We analyzed the developmental stage-specificity of this apoptosis using double staining by in situ nick end labeling and immunohistochemistry against three proteins expressed at specific stages of granule neuron development. The amount of apoptosis of EGL neurons peaked on postnatal day 9. In the 9-day-old rat cerebellum, 54.0% of apoptotic EGL neurons expressed proliferating cell nuclear antigen. On the other hand, 22.2 and 15.4% of apoptotic EGL neurons existed in the postmitotic and premigratory zone defined by expression of TAG-1 and 440 kDa ankyrinB, respectively. Thus, proliferative granule neurons undergo apoptosis more frequently than postmitotic granule neurons in EGL of the developing cerebellum. This suggests that there are developmental stage-specific mechanisms of apoptosis of cerebellar granule neurons.