Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons.
Axonal transection of adult sympathetic and sensory neurons leads to a decrease in their content of target-derived nerve growth factor (NGF) and to dramatic changes in the expression of several neuropeptides and enzymes involved in transmitter biosynthesis. For example, axotomy of sympathetic neurons in the superior cervical ganglion (SCG) dramatically increases levels of galanin, vasoactive intestinal peptide (VIP), and substance P and their respective mRNAs and decreases mRNA levels for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Axotomy of sensory neurons in lumbar dorsal root ganglia (DRG) increases protein and mRNA levels for galanin and VIP and decreases levels for substance P and calcitonin gene-related peptide (CGRP). To assess whether reduction in the availability of endogenous NGF might play an important role in triggering these changes, we injected nonoperated animals with an antiserum against NGF (alphaNGF). alphaNGF increased levels of peptide and mRNA for galanin and VIP in neurons in both the SCG and DRG. NPY protein and mRNA were decreased in the SCG, but levels of TH protein and mRNA remained unchanged. In sensory neurons the levels of SP and CGRP protein decreased after alphaNGF treatment. These data suggest that the reduction in levels of NGF in sympathetic and sensory neurons after axotomy is partly responsible for the subsequent changes in neuropeptide expression. Thus, the peptide phenotype of these axotomized neurons is regulated both by the induction of an "injury factor," leukemia inhibitory factor, as shown previously, and by the reduction in a target-derived growth factor.
Shadiack
A M
AM
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4975, USA.
Sun
Y
Y
Zigmond
R E
RE
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology*; D066298:In Vitro Techniques; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D006131:Growth Inhibitors; D007106:Immune Sera; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009478:Neuropeptide Y; D009479:Neuropeptides; D020933:Neurotrophin 3; D012333:RNA, Messenger; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D019004:Galanin; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide