Nerve Growth Factors and Neurotrophins

Cell division, cell death, and cell differentiation are hallmarks of embryogenesis. Such processes are supported by neurotrophins that have the capacity of regulating not only developmental processes, but also neuronal survival, morphological adaptation, and neural plasticity. Nerve growth factor (NGF) is a prototype of neurotrophins capable of influencing survival and differentiation of neuronal cells during development. It has been shown that the cholinergic neurons of the basal forebrain critically depend on NGF for differentiation and survival. Exogenous administrations of NGF induced up or down regulation of cholinergic enzymatic activity that in turn altered the number of muscarinic receptors. Apart from its trophic function through activation of tyrosine kinase A receptors, NGF also can be neurotoxic through activation of p75 NTR receptors. Such dual and opposite effect suggests that exogenous NGF supplementation could alter the exact maturation of the cholinergic system either in a positive or in a negative way, depending on the period of the treatment. This was confirmed with NGF treatment during postnatal week two generating an adult-like spatial learning capacity despite animals being less than 5 weeks old. This superiority was maintained into adulthood. By contrast, NGF treatment during postnatal week one impaired spatial learning and hindered development into adult-like efficiency. These results reveal a developmentally crucial period for spatial learning mechanisms with a critical modulatory role of NGF.