title: The p75 neurotrophin receptor has nonapoptotic antineurotrophic actions in the basal forebrain.
abstract: Because of controversy about the role of the p75 neurotrophin receptor (p75(NTR) ) in the cholinergic basal forebrain (CBF), we investigated this region in p75(NTR) third exon knockout mice that were congenic with 129/Sv controls. They express a shortened intracellular form of p75(NTR) , permitting detection of p75(NTR) -expressing cells. We performed separate counts of choline acetyltransferase (ChAT)-expressing and p75(NTR) -expressing neurons. In agreement with past reports, the number of ChAT-immunoreactive neurons in knockout mice was greater than in wild-type mice, and this was evident in each of the main anatomical divisions of the CBF. In contrast, the number of p75(NTR) -immunoreactive neurons did not differ between genotypes. The biggest increase in ChAT neurons (27%) was in the horizontal limb of the diagonal band of Broca (HDB), in which region the number of p75(NTR) -positive neurons was unchanged. Double staining revealed that some neurons in wild-type mice expressed p75(NTR) but not ChAT. In the knockout mice, all p75(NTR) -expressing neurons expressed ChAT. The increase in cholinergic neurons, therefore, was at least partially attributable to a higher proportion of ChAT immunoreactivity within the population of p75(NTR) -expressing neurons. Cholinergic neurons were also larger in knockout mice than in controls. In the hippocampal CA1 region, knockout mice had a greater number of cholinergic fibers. There was a 77% increase in hippocampal ChAT activity in knockout mice and a 38% increase in heterozygotes. The data do not support an apoptotic role but indicate a broad antineurotrophic role of p75(NTR) in the cholinergic basal forebrain.
authors.affiliation: Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ursula
authors.initials: U
authors.lastname: Greferath
authors.forename: Jennifer
authors.initials: J
authors.lastname: Trieu
authors.forename: Graham L
authors.initials: GL
authors.lastname: Barrett
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D048429:Cell Size; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000502:physiology; D059329:Cholinergic Neurons / Q000378:metabolism*; D020667:Diagonal Band of Broca / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016548:Prosencephalon / Q000166:cytology; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism*
chemical_list: D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase