BCL-XL PROTECTS ADULT SEPTAL CHOLINERGIC NEURONS FROM AXOTOMIZED CELL-DEATH

Bcl-xL suppresses apoptotic cell death induced by diverse stimuli in c ell lines in vitro. To examine the mechanism by which axotomized choli nergic neurons die in vivo, lentiviral vectors expressing Bcl-xL, huma n nerve growth factor (hNGF), or green fluorescent protein were inject ed into the septum 3 weeks before transection of the fimbria fornix. T hree weeks after transection, Bcl-xL- and hNGF-injected animals showed significantly higher numbers of spared cholinergic neurons compared w ith control (green fluorescent protein) injected animals. These result s provide evidence that adult axotomized cholinergic neurons die of ap optotic death that can be prevented by local delivery of hNGF or intra cellular delivery of Bcl-xL.