The p75 neurotrophin receptor has nonapoptotic antineurotrophic actions in the basal forebrain

Because of controversy about the role of the p75 neurotrophin receptor (p75NTR) in the cholinergic basal forebrain (CBF), we investigated this region in p75NTR third exon knockout mice that were congenic with 129/Sv controls. They express a shortened intracellular form of p75NTR, permitting detection of p75NTR-expressing cells. We performed separate counts of choline acetyltransferase (ChAT)-expressing and p75NTR-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 p75NTR-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 p75NTR-positive neurons was unchanged. Double staining revealed that some neurons in wild-type mice expressed p75NTR but not ChAT. In the knockout mice, all p75NTR-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 p75NTR-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 p75NTR in the cholinergic basal forebrain. (c) 2011 Wiley Periodicals, Inc.