Apoptosis and Bcl-2 oncoprotein expression in the human fetal central nervous system

Apoptosis and the apoptosis-regulatory gene bcl-2 have been suggested from animal studies to be important during the development of the central nervous system (CNS), but information on apoptotic activities of the developing human CNS has been scarce. To establish spatial and temporal distributions of apoptotic cells and Bcl-2 oncoprotein expression, we examined sections taken from cerebral cortex, hippocampus and brainstem at weeks 14, 18, 27, and 32 of gestation. Terminal transferase-mediated nick end labelling (TUNEL), histological analyses, and immunocytochemical staining using monoclonal antibodies were employed. Except for layer I of the motor cortex and the molecular layer of the hippocampus, both at week 14 of gestation, TUNEL-positive cells with typical apoptotic appearance and apoptotic indices, ranging from 0.08 to 2.85, were found in all other brain regions examined including visual, sensory, frontal and motor cortices, hippocampus, dorsal raphe, locus coeruleus, and periaqueductal grey of the brainstem. No specific spatial or temporal distribution patterns of apoptotic cells were found in the cortices. However, the apoptotic index of the molecular layer of the hippocampus increased with the gestation age. The periaqueductal grey of the brainstem showed high apoptotic indices (ranging from 0.37 to 2.85) at all the gestation ages studied. An inverse correlation between apoptosis and Bcl-2 oncoprotein expression was found in visual, sensory, and motor cortices but not in the frontal cortex and hippocampus. Apoptosis and Bcl-2 oncoproteins are important for CNS development and, apart from being an apoptosis regulator, Bcl-2 oncoproteins may also have other roles to play during neural development.