Neuronotrophic factors in cellular functional and cognitive repair of adult brain.

Neuronotrophic factors (NTFs) are special proteins that control survival, growth and functional competence of selected neuronal populations during their development. A recently articulated CNS neuronotrophic hypothesis proposes that adult central neurons continue to be dependent on endogenous supplies of their NTFs for maintenance, function and repair capabilities. The hypothesis has important implications in two major neurologic areas:i) involutive and degenerative processes and ii) CNS regeneration. Strong evidence favoring this general hypothesis has come from the recently observed effects of Nerve Growth Factor (NGF) on the forebrain cholinergic neurons in adult rats. Medial septum cholinergic (MSC) neuros project to the hippocampal formation largely via the fimbria-fornix tract. Transection of the fimbria-fornix interrupts the retrograde delivery of hippocampal NGF to the MSC neuronal somata, leading to reduction in their cholinergic enzyme and, possibly, progressive cellular atrophy. Intraventricular administration of exogenous NGF compensates for the loss of endogenous NGF supply and can reverse as well as protect against the neuronal damage. In a second model, intraventricular NGF infusions were applied to 2-year old (aged) rats displaying a deficient cognitive behavior. Four-weeks administration resulted in i) a correction of the cognitive deficit and ii) a increased body size of basal forebrain cholinergic neurons Cholinergic deficits are known to accompany cognitive deficits both in the brain aging process and Alzheimer's disease. The NGF effects on aged rats, therefore, strongly encourage the possibility of future clinical application in both such cases of brain dysfunction.