Unaltered expression of Fas (CD95/APO-1), Caspase-3, Bel-2 and Annexins inbrains of fetal Down syndrome: evidence against increased apoptosis

Apoptosis is the mechanism by which cells are programmed to die under a wid e range of physiological and developmental stimuli. Accumulating evidence i ndicates that enhanced apoptosis (programmed cell death) in Down syndrome ( DS) may play a role in mental retardation and precocious neurodegeneration of the Alzheimer-type. In this regard, alteration of several apoptosis rela ted proteins have been reported in adult DS brain. Fetal DS neurons exhibit ed increased reactive oxygen species leading to early apoptosis, however, e xpression of apoptosis related proteins in fetal DS, has never been conside red. To address this issue, we investigated the expression of proteins invo lved in apoptosis including Fas (CD95, APO-1), caspase-3, Bcl-2 and annexin s in the cerebral cortex of control and DS fetal brain by western blot and two dimensional electrophoresis. Here, we report that no detectable changes were obtained in fetal DS brain in the expression of Fas, caspase-3, Bcl-2 and Annexins (I, II, V, and VI) compared to controls. In parallel experime nt, we also examined the expression of neuron specific enolase (NSE), a neu ronal marker found to be decreased in adult DS brain, to see if there is an y neuronal loss and no difference was observed between the two groups. Prot ein expression did not correlate with age. The unchanged levels of Fas, Bcl -2 and annexins together with unaltered caspase-3 expression, a predominant caspase that executes apoptosis in the developing nervous system, suggest that enhanced apoptosis may not be apparent in fetal DS brain as demonstrat ed for adult DS brain.