Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation.
Emerging evidence suggests that the p75 neurotrophin receptor (p75NTR) mediates cell death; however, it is not known whether p75NTR negatively regulates other neuronal phenotypes. We found that mice null for p75NTR displayed highly significant increases in the size of basal forebrain cholinergic neurons, including those that are TrkA-positive. Cholinergic hippocampal target innervation also was increased significantly. Activity of the cholinergic neurotransmitter synthetic enzyme choline acetyltransferase (ChAT) was increased in both the medial septum and hippocampus. Upregulation of these cholinergic features was not associated with increased basal forebrain or hippocampal target NGF levels. In contrast, striatal cholinergic neurons, which do not express p75NTR, showed no difference in neuronal number, size, or ChAT activity between wild-type and p75NTR null mutant mice. These findings indicate that p75NTR negatively regulates cholinergic neuronal phenotype of the basal forebrain cholinergic neurons, including cell size, target innervation, and neurotransmitter synthesis.
Yeo
T T
TT
Department of Neurology, University of California at San Francisco/Veterans Affairs Medical Center, San Francisco, California 94121, USA.
Chua-Couzens
J
J
Butcher
L L
LL
Bredesen
D E
DE
Cooper
J D
JD
Valletta
J S
JS
Mobley
W C
WC
Longo
F M
FM
D000818:Animals; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003342:Corpus Striatum / Q000473:pathology; D018628:Gene Dosage; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006984:Hypertrophy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010275:Parasympathetic Nervous System / Q000473:pathology*; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D012688:Septum Pellucidum / Q000378:metabolism
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA