P75 nerve growth factor receptor is important for retrograde transport of neurotrophins in adult cholinergic basal forebrain neurons

The role of the p75 nerve growth factor receptor in the retrograde transpor t of neurotrophins in the adult CNS was investigated by comparing the trans port of I-125-labeled neurotrophins by normal and p75 nerve growth factor r eceptor-deficient cholinergic septohippocampal neurons. In control mice, ne rve growth factor was selectively transported from the hippocampal formatio n to the cholinergic neurons in the septum. Nerve growth factor labeling wa s found in three to four times as many septal cholinergic neuronal cell bod ies than labeling for neurotrophin-3 or neurotrophin-4/5, and transported b rain-derived neurotrophic factor was barely detectable. Cells were consider ed as labeled when the number of grains per cell exceeded five times backgr ound. In p75 nerve growth factor receptor-deficient mice, the number of cho linergic neurons labeled with each of the neurotrophins was reduced by 85-9 5%. Retrograde labeling of septohippocampal neurons with Fluorogold was not obviously reduced in p75 nerve growth factor receptor-deficient mice, sugg esting that general transport mechanisms were not impaired. Despite the red uced neurotrophin transport, cholinergic neurons of p75 nerve growth factor receptor-deficient mice were larger than controls and had an apparently no rmal density of immunostaining for choline acetyltransferase. Since nerve g rowth factor is reportedly involved in size regulation and choline acetyltr ansferase expression, this raises the possibility that the retrograde trans port itself is not essential for these events. Thus, p75 nerve growth factor receptor plays an important, although not exc lusive, role in the transport of neurotrophins by cholinergic basal forebra in neurons, and retrograde transport of nerve growth factor may not be need ed for regulating certain cellular processes. (C) 1999 LBRO. Published by E lsevier Science Ltd.