Axotomy alters neurotrophin and neurotrophin receptor mRNAs in the vagus nerve and nodose ganglion of the rat.
Neurotrophins and neurotrophin receptors play an important role in survival and growth of injured peripheral nerves. To study the injury-mediated neurotrophic response in autonomic nerves, we investigated changes in mRNA expression of neurotrophins and their receptors in the transected vagus nerve and nodose ganglion. Studies using in situ hybridization histochemistry showed that axotomy of the cervical vagus nerve resulted in increased expression of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and for TrkA, TrkB, and TrkC receptors in non-neuronal cells at both the proximal and distal segments of the transected cervical vagus nerve. Moreover, NGF protein was increased in the distal end, and NT-3 protein was increased in both the proximal and the distal ends of the transected nerve 3 days after axotomy. No change of p75(NTR) mRNA was detected in the transected vagus nerve. The induction of each neurotrophin and Trk receptor mRNA was apparent within 1 day after the axotomy and was sustained at least 14 days. By 45 days after the axotomy, a time when axonal reconnection with target tissue is made (integrity of the nerve-target connection was confirmed by the retrograde transport of FluoroGold from the stomach to vagal cell bodies), the levels of neurotrophin and Trk mRNAs in the vagus nerve declined to pre-axotomy levels. TrkA, TrkC, and p75(NTR) mRNA-containing vagal sensory neurons in the nodose ganglion were reduced in number after cervical vagotomy. Neurotrophin-mRNA-containing neurons were not found in the nodose ganglia from either intact or vagotomized rats. The axotomy-induced up-regulation of neurotrophins and Trk receptors mainly in the non-neuronal cells at or near the site of transection suggests that neurotrophins are involved in the survival and regeneration process of the vagus nerve after injury.
Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA.
P
P
Lee
H
H
Zhuo
C J
CJ
Helke
D000818:Animals; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology; D020933:Neurotrophin 3 / Q000032:analysis / Q000235:genetics*; D009620:Nodose Ganglion / Q000737:chemistry / Q000293:injuries / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000235:genetics; D020917:Receptor, trkA / Q000235:genetics; D020813:Receptor, trkB / Q000235:genetics; D020812:Receptor, trkC / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC