PROTECTIVE EFFECTS OF BDNF AND NT-3 BUT NOT PDGF AGAINST HYPOGLYCEMICINJURY TO CULTURED STRIATAL NEURONS

Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and p latelet-derived growth factor (PDGF) exert trophic effects on striatal neurons in vitro, which raises the possibility that these growth fact ors might also counteract neuronal death provoked by various insults. We have found that BDNF and NT-3, but neither PDGF-AA nor -BB, added 2 4 h before the insult ameliorated hypoglycemic neuronal damage induced by 15 or 24 h of glucose deprivation in rat striatal cell cultures. B DNF and NT-3 afforded neuronal protection even when administered 8 or 4 h, respectively, after the onset of hypoglycemia. In normoglycemic s triatal cultures exposed to these neurotrophins for several days, ther e was a slight, nonsignificant increase of the number of surviving mic rotubule-associated protein-2-positive cells (20-30%) compared to untr eated control cultures, but no change of glial cells. Exposure of the cultures to BDNF or NT-3 produced a significant increase in the number of neurons expressing detectable levels of the calcium-binding protei n, calbindin, suggesting that a stabilization of calcium homeostasis m ight be implicated in the neuroprotection. Immunocytochemical analysis revealed that the majority (70-80%) of neurons in the striatal cultur es expressed TrkB and TrkC, the functional receptors for BDNF and NT-3 , respectively, implying that the effects of the neurotrophins are mos t likely direct. These data indicate that BDNF and NT-3 can protect st riatal neurons against hypoglycemia in vitro and raise the possibility that these neurotrophins could counteract striatal neuronal death ind uced by hypoglycemic and ischemic insults in vivo. (C) 1995 Academic P ress, Inc.