PROTECTION BY PROSAPOSIN AGAINST ISCHEMIA-INDUCED LEARNING-DISABILITYAND NEURONAL LOSS

Prosaposin, the protein precursor of saposins A; B, C, and D which act ivate sphingolipid hydrolases, is abundant in several brain regions in cluding the hippocampus. We infused prosaposin continuously for 7 days into the lateral ventricle of gerbils starting 3 hours before 3-min o f forebrain ischemia. Using the step-down passive avoidance task, we d emonstrated that ischemia-induced learning disability is prevented alm ost completely by prosaposin infusion. Subsequent light and electron m icroscopic examinations showed that pyramidal neurons in the CA1 field of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the field were significantly more num erous in gerbils infused with prosaposin infusion than in those receiv ing saline infusion. These findings suggest that prosaposin possesses neurotrotrophic activity to protect hippocampal CA1 neurons from letha l ischemic damage. (C) 1994 Academic Press, Inc.