Recovery of ChAT immunoreactivity in axotomized rat cholinergic septal neurons despite reduced NGF receptor expression.
Previous studies have suggested that target-derived nerve growth factor (NGF) is essential for the survival of cholinergic basal forebrain neurons. Thus, axotomy of septohippocampal neurons in adult rats resulting in the withdrawal of target-derived NGF caused a dramatic loss of choline acetyltransferase (ChAT)-immunoreactive neurons in the medial septum-diagonal band complex. We have recently shown that this loss of immunolabelled neurons does not indicate cell death, since many septohippocampal cholinergic neurons recover their immunoreactivity for ChAT after a long survival time despite disconnection from target-derived neurotrophins. One possibility would be that these surviving ChAT-immunoreactive neurons have gained access to other, probably local, NGF sources. Here we provide evidence that the recovery of ChAT immunoreactivity after axotomy is not accompanied by a similar recovery of NGF receptor expression in these neurons. In situ hybridization for p75NTR mRNA and trkA mRNA 6 months after bilateral fimbria-fornix transection revealed a substantial loss of labelled cells. In addition, there was a persisting loss of p75NTR-immunoreactive and NGF-immunoreactive medial septal neurons. Cholinergic neurons in controls did not express NGF mRNA, but were heavily immunostained for NGF protein due to receptor-mediated uptake. These data suggest that at least some cholinergic septohippocampal neurons re-express ChAT either independently of NGF or with a reduced need for NGF.
Naumann
T
T
Institute of Anatomy, University of Freiburg, Germany.
Straube
A
A
Frotscher
M
M
D000818:Animals; D001369:Axons / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003714:Denervation; D005260:Female; D007158:Immunologic Techniques; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012688:Septum Pellucidum / Q000166:cytology / Q000378:metabolism*
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D002795:Choline O-Acetyltransferase