Is there nicotinic modulation of nerve growth factor? Implications for cholinergic therapies in Alzheimer's disease

Studies on the neurobiology of nerve growth factor (NGF) reveal a diverse r ange of actions. Through alterations in gene expression, NGF is important i n maintaining and regulating the phenotype of neurons that express the high -affinity receptor, trkA. Nerve growth factor also has a rapid action, reve aled by its role in pain signaling in bladder and in skin. In the central n ervous system (CNS), NGF has an intimate relationship with the cholinergic system. It promotes cholinergic neuron survival after experimental injury b ut also maintains and regulates the phenotype of uninjured cholinergic neur ons. In addition to these effects mediated by gene expression, NGF has a ra pid neurotransmitter-like action to regulate cholinergic neurotransmission and neuronal excitability. Consistent with its actions on the cholinergic s ystem, NGF can enhance function in animals with cholinergic lesions and has been proposed to be useful in humans with Alzheimer's disease (AD); howeve r, the problems of CNS delivery and side effects (particularly pain) limit the clinical efficacy of NGF. Drug treatment strategies to enhance producti on of NGF in the CNS may be useful in the treatment of AD. Nicotine is one such agent, which, when administered directly to the hippocampus in rats, p roduces long-lasting elevation of NGF production. (C) 2001 Society of Biolo gical Psychiatry.