Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice.
The functions of the low-affinity p75 nerve growth factor receptor (p75(NGFR)) 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 p75(NGFR)-deficient mice or in normal mice systemically injected with a p75(NGFR)-inhibiting peptide. Control, but not p75(NGFR)-deficient, mice also had fewer cholinergic striatal interneurons. Apparently, p75(NGFR) mediates apoptosis of these developing neurons in the absence of TrkA, and modulation of p75(NGFR) can promote neuronal survival. Cholinergic basal forebrain neurons are involved in learning and memory.
Van der Zee
C E
CE
Department of Anatomy and Neurobiology, Tupper Building, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada. thagg@is.dal.ca
Ross
G M
GM
Riopelle
R J
RJ
Hagg
T
T
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D053938:DNA Fragmentation; D007395:Interneurons / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017072:Neostriatum / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000166:cytology*; D010766:Phosphorylation; D016548:Prosencephalon / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA