CHANGES IN BETA-AMYLOID PRECURSOR PROTEIN SECRETION ASSOCIATED WITH THE PROLIFERATIVE STATUS OF CNS DERIVED PROGENITOR CELLS

We characterized the secretion of amyloid precursor protein (APP) in r at primary neurons and conditionally immortalized central nervous syst em (CNS) derived progenitor cell lines, to evaluate their suitability as models for studies on APP metabolism. We observed that primary cell s dissociated from different regions of the embryonic brain secreted p rogressively more APP during in vitro maturation. The increase in basa l secretion resulted in an offset of the response to protein kinase C (PKC) activated secretion and was correlated with an increased PKC alp ha expression. The same type of analysis was performed on CNS derived conditionally immortalized cells whose growth potential becomes restri cted upon shifting of the culture conditions to a non-permissive tempe rature (39 degrees C), an event that coincides with their progression toward differentiation. With a pattern consistent with that observed i n primary neurons, conditionally immortalized cells exposed to 39 degr ees C showed an offset of the secretory response to activation by PdBu and also an increased expression of PKC alpha. These data suggest tha t APP secretion and its regulation in CNS derived cells is influenced by the proliferative status of the cells.