Complete deletion of the neurotrophin receptor p75NTR leads to long-lasting increases in the number of basal forebrain cholinergic neurons.
Cholinergic neurons innervating cortical structures are among the most affected neuronal populations in Alzheimer's disease. In rodents, they express high levels of the neurotrophin receptor p75NTR. We have analyzed cholinergic septohippocampal neurons of the medial septal nucleus in p75exonIII (partial p75NTR knock-out) and p75exonIV (complete p75NTR knock-out) mice, in their original genetic background and in congenic strains. At postnatal day 15, the p75exonIII mutation leads to a moderate increase (+13%) in these neurons among littermates only after back-crossing in a C57BL/6 background. In contrast, the null p75exonIV mutation, which prevents expression of both the full-length and the shorter p75NTR isoforms, results in a 28% neuronal increase, independent of genetic background. The incomplete nature of the p75NTR mutation used previously, coupled with difficulties in delineating the mouse medial septum and the impact of the genetic background on cell numbers, all contribute to explain previous difficulties in establishing the role of p75NTR in regulating cholinergic neuron numbers in the mouse forebrain.
Naumann
Thomas
T
Institute of Anatomy, University of Freiburg, D-79104 Freiburg, Germany. naumannt@uni-freiburg.de
Casademunt
Elisabeth
E
Hollerbach
Ewald
E
Hofmann
Jutta
J
Dechant
Georg
G
Frotscher
Michael
M
Barde
Yves-Alain
YA
D000109:Acetylcholine / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002452:Cell Count / Q000706:statistics & numerical data; D003433:Crosses, Genetic; D005091:Exons; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D020665:Septum of Brain / Q000166:cytology / Q000378:metabolism; D013045:Species Specificity
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000109:Acetylcholine