Rat mature sympathetic neurones derive neurotrophin 3 from peripheral effector tissues.
In a previous study we have demonstrated that endogenous neurotrophin 3 (NT3) is required for the survival of most sympathetic neurones in postnatal rats. However, the mechanisms underlying the action of NT3 on sympathetic neurones is not known. Neither is it understood whether NT3 is retrogradely transported from peripheral tissues or acts locally in an autocrine fashion. In the present study, NT3-mRNA was quantified in sympathetic effector tissues and NT3 protein was localized in intact and lesioned sympathetic nerves in rats. NT3-mRNA is expressed and developmentally regulated in many effector tissues including mesenteric arteries, salivary gland, heart and kidney but hardly detectable in the superior cervical ganglia of adult animals. The majority of sympathetic neurones express immunoreactivity for TrkA and TrkC in both neonatal and adult rats. Sympathetic somata are normally immunoreactive for NT3, but the immunoreactivity is abolished by systemic administration of NT3 antibodies or axotomy of postganglionic neurones, suggesting an accumulation of NT3 from extraneuronal sources. Furthermore, the detection of NT3-immunoreactivity in the internal carotid nerve as early as 3 h following a compression and only on the distal side indicates endogenous NT3 is retrogradely transported by sympathetic neurones. These studies provide evidence indicating that NT3, like nerve growth factor, is an effector tissue-derived neurotrophic factor for sympathetic neurones both during development and in the adult animal. Thus, we have provided a clear example that one type of neurone derives, through a retrograde transport mechanism, two neurotrophic factors simultaneously from its peripheral effector tissues.
Zhou
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Department of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, Adelaide. pzxfz@cc.flinders.edu.au
Chie
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Deng
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Rush
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RA
D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001370:Axonal Transport / Q000502:physiology*; D019771:Axotomy; D003429:Cross Reactions; D005260:Female; D008297:Male; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D020933:Neurotrophin 3; D010525:Peripheral Nerves / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D020917:Receptor, trkA; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D012756:Sheep; D017783:Superior Cervical Ganglion / Q000166:cytology; D014158:Transcription, Genetic / Q000502:physiology
D000906:Antibodies; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC