Basal Forebrain Neuronal Loss in Mice Lacking Neurotrophin Receptor p75

摘要

There is substantial evidence from in vitro studies that nerve growth factor (NGF) exerts an important influence on the development and survival of central neurons. The effects of NGF are thought to be mediated through the high-affinity tyrosine receptor kinase trkA and the low-affinity p75 receptor. Several studies suggest that the p75 receptor initiates an apoptotic signal that leads to neuronal death. The role of NGF in the development and survival of central neurons in intact systems is less clear. The use of'null mutant mice provides a useful strategy for delineating the role of specific receptors and factors during in vivo development. Mice that are deficient in NGF and trkA have been produced, and the effect of the mutation on central neurons was investigated. Despite the observation of impairment of peripheral neuronal development, neither the lack of NGF nor the absence of trkA receptors prevented the development and survival of septal cholin-ergic neurons, cells that normally express trkA and p75 receptors and that can be rescued by the administration of NGF after traumatic lesion. These two studies, however, did not provide quantitative data.