Rat heart GDNF: effect of chemical sympathectomy.
Developmental studies indicate a role for GDNF in survival of motor, autonomic, and sensory neurons. However, no study attempted to demonstrate its participation in autonomic nerve regeneration. In this work, chemical sympathectomy by 6-hydroxydopamine provided the model for assessing heart GDNF expression during denervation and axonal regrowth. A glyoxylic acid-based histochemical technique evaluated the noradrenergic innervation. ELISA determined GDNF levels after concentrating heart homogenates. Light and ultrastructural in situ hybridization and immunocytochemistry were used for identifying cells expressing GDNF mRNA and protein. In control rats, the GDNF cardiac levels were significantly higher in 37-day-old animals in comparison with those aging 60 days. In sympathectomized rats, GDNF cardiac levels were significantly higher 7 days after sympathectomy and dropped to control levels at day 30. GDNF mRNA was expressed in atrial and ventricular myocytes from normal and sympathectomized rats. GDNF immunoreactivity occurred on atrial granules and quantitative analysis in electron micrographs confirmed ELISA-obtained data. In ventricular myocytes gold particles occurred sparsely. These findings constitute the first evidence for GDNF synthesis by cardiomyocytes and postulate a role for this factor soon after cardiac sympathetic denervation, probably in nerve regeneration. In atrial myocytes, GDNF is probably secreted by regulated pathway.
Martinelli
Patricia M
PM
Department of Morphology, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), 31270-901 Belo Horizonte, MG, Brazil.
Camargos
Elizabeth R S
ER
Morel
Gérard
G
Tavares
Carlos A P
CA
Nagib
Patrícia R A
PR
Machado
Conceição R S
CR
D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D006325:Heart Atria / Q000294:innervation / Q000648:ultrastructure; D006352:Heart Ventricles / Q000294:innervation / Q000648:ultrastructure; D017403:In Situ Hybridization; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration; D018696:Neuroprotective Agents / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000737:chemistry; D016627:Oxidopamine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016627:Oxidopamine