Survival of Cholinergic Forebrain Neurons in Developing p75NGFR-Deficient Mice

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Science  06 Dec 1996:
Vol. 274, Issue 5293, pp. 1729-1732
DOI: 10.1126/science.274.5293.1729


The functions of the low-affinity p75 nerve growth factor receptor (p75NGFR) in the central nervous system were explored in vivo. In normal mice, approximately 25 percent of the cholinergic basal forebrain neurons did not express TrkA and died between postnatal day 6 and 15. This loss did not occur in p75NGFR-deficient mice or in normal mice systemically injected with a p75NGFR-inhibiting peptide. Control, but not p75NGFR-deficient, mice also had fewer cholinergic striatal interneurons. Apparently, p75NGFR mediates apoptosis of these developing neurons in the absence of TrkA, and modulation of p75NGFR can promote neuronal survival. Cholinergic basal forebrain neurons are involved in learning and memory.

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