Apoptosis of undifferentiated progenitors and granule cell precursors in the postnatal human cerebellar cortex correlates with expression of BCL‐2, ICE, and CPP32 proteins

Abstract

Naturally occurring apoptotic cells have been demonstrated in the postnatal cerebellum of rodents (Wood et al. [1993] Neuron 11:621-632; Krueger et al. [1995] J. Neurosci. 15:3366-3374). The nature of these cells differs among species: they are considered to be granule cells in mouse and astrocytes in rat. We labeled proliferating and apoptotic cells in the postnatal human cerebellar cortex by using antibodies against the Ki-67/proliferating cell nuclear antigen and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method for fragmented DNA. We also immunocytochemically detected some proteins encoded by genes modulating apoptosis and specific markers of neuronal/glial differentiation. Proliferating cells were observed from birth to 4 months, representing 31-35% of cells within the external granular layer (EGL). Apoptotic cells were detected during the first 3 months and corresponded to 5-7% of EGL cells. Much lower percentages were calculated in other cortical layers and white matter. The balance between proliferation and apoptosis was quantitatively favorable to the latter during the first postnatal week. Expression of BCL-2, CPP32, and interleukin-1beta-converting enzyme (ICE) proteins was spatially and developmentally regulated in parallel with apoptosis. Apoptotic cells were often CPP32/ICE immunoreactive but negative for BCL-2. Some apoptotic cells were positive for vimentin and, less frequently, for alpha-internexin or type-III beta tubulin, but never expressed the glial fibrillary acidic protein. This study demonstrates that apoptosis is a significant phenomenon in early postnatal development of human cerebellar cortex and shares some of the regulatory mechanisms described in other vertebrates.

Cell proliferation and death in the brain of active and hibernating frogs

“…Proliferation and cell death appear to be a binomium characterizing adult neurogenesis, similar to that of normal developmental neurogenesis (Lossi et al. 1998; Lossi & Merighi, 2003).…”

“…normal developmental neurogenesis (Lossi et al 1998;Lossi & Merighi, 2003). It is generally believed that a correct balance between cell proliferation and apoptosis during development is fundamental to determine the ultimate architecture of tissues and organs.…”

“…In the maturation of the CNS, neurogenic events are regulated by cell death, which assures the number and distribution of neurons in the brain network (Lossi et al 1998;Lossi & Merighi, 2003). More generally, a precise balance of cell production and cell death is required to maintain an accurate number of cells in regenerative tissues.…”

Astn2, A Novel Member of the Astrotactin Gene Family, Regulates the Trafficking of ASTN1 during Glial-Guided Neuronal Migration

“…To assay for apoptosis, organotypic slice cultures were incubated with the pCX retrovirus containing Venus cDNA and treated with DMSO or with DMSO and Dynasore (40 or 80 µM final concentration) as above, then were processed for immunohistochemistry as described below and stained with sheep anti-GFP and rabbit anti-Caspase 3 antibodies (Lossi et al, 1998). The number of cells that were double-labeled with anti-GFP and anti-Caspase 3 antibodies were counted per unit area (Adams et al, 2002).…”

Cell Death in Mammalian Development

“…Apoptosis induced by NGF withdrawal decides the number of developing neurons [115][116][117]. In most mammals such as rats, mice, rabbits and humans most of the cerebellar development and apoptotic cell death occur during the first weeks after birth [121,122]. In mouse embryos there is a peak of cell death (70%) between E10-E18 at the cortical region of the brain and this cell death subsequently declines to 50% between E14-E18 [119].…”