Regulators of Neuronal Survival (BcI-2, Bax, c-Jun) in Prenatal and Postnatal Human Frontal and Temporal Lobes in Normal and Down Syndrome Brain

Abstract

Although the molecular basis of programmed cell death, a pivotal process for the proper development, organization and future functioning of the brain, has been studied extensively in different experimental models and in various species, it is not entirely understood. The principles that govern this process in the developing human brain are even less elucidated. To provide more insight into the mechanisms underlying programmed cell death in the human brain, we have studied the temporal and spatial pattern of immunolocalization in the developing normal and Down syndrome brain of two proteins that are supposed to act either as a neuronal survival promoter-Bcl-2 or a neuronal survival suppressor- Bax. Our data show a dramatic decrease in immunoreactivity to Bcl-2 and, at the same time, a gradual increase in immunoreactivity to Bax in the human brain around 30-32 week’s gestation; according to recent data, this gestational period is accompanied by the most intense reduction of cortical neurons. However, our obser vations also suggest that at least at certain stages of human brain development, both proteins, and especially Bax, may also be involved in the final differentiation and maturation of central nervous system neurons. In addition, altered patterns of Bcl-2 and, to a much lesser degree, also of Bax immunoreactivity in developing Down syndrome brain allow us to propose that mechanisms underlying programmed cell death may contribute to the pathology in Down syndrome brain.