Correlation of Cholinergic Functional Stimulation by Exogenous NGF with Aged Rat Behavior

The neurotrophic protein known as nerve growth factor (NGF, Levi-Montalcini, 1987) has recently been shown to have profound effects on the survival and transmitter function of central cholinergic neurons in both the basal forebrain and striatum of neonatal rodents, and adult rodents and primates (Whittemore and Sciger, 1987; Williams et al., 1989, Tuszynski et al., 1990, and Koliatsos, this volume). From such animal research has evolved the clinical hypothesis that NGF therapy would ameliorate the behavioral impairments associated with age-related cholinergic dysfunction, particularly Alzheimer’s disease (AD, Hefti and Weiner, 1986; Phelps et al., 1989). Still, many questions remain concerning the mechanisms of acetylcholine (ACh) homeostasis in the brain, and the specific behaviors mediated by central cholinergic pathways that are affected by Alzheimer’s disease. Also unknown is the full extent of NGF’s effects on both cholinergic and non-cholinergic neuronal systems.