Martinelli Patrícia Massara, Camargos Elizabeth Ribeiro da Silva, Azevedo Andréa Alves, Chiari Egler, Morel Gérard, Machado Conceição Ribeiro da Silva
Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil.
Auton Neurosci. 2006 Dec 30;130(1-2):32-40. doi: 10.1016/j.autneu.2006.05.004. Epub 2006 Jul 18.
In rats, autonomic nerve endings are damaged during Trypanosoma cruzi-induced myocarditis. Gradual recovery occurs after the acute phase. The present work shows the cardiac levels of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF), and their cellular sources during T. cruzi infection in rats. Atrial and ventricular NGF levels (ELISA) increased significantly at day 20 post inoculation, the time-point of maximal sympathetic denervation. ELISA failed to show significant increase of cardiac GDNF levels. However immunohistochemistry showed a significant increase of anti-GDNF gold particles over atrial granules at day 20. Light microscopy showed stronger NGF immunostaining in atrial cardiomyocytes and several blood capillaries. In situ hybridization showed NGF and GDNF mRNAs in atrial and ventricular myocytes of both infected and uninfected animals. Endothelial cells exhibited NGF mRNA and protein only in infected rats. No evidence of neurotrophic factor expression by the infiltrating mononuclear cells was found. This is the first report on neurotrophic factor expression during T. cruzi infection. Our findings indicate an important role for NGF in the regenerative phenomena subsequent to a myocarditis able to damage sympathetic nerve endings, with preservation of preterminals and nerve trunks. GDNF could have a minor or a more transient participation.
在大鼠中,克氏锥虫诱导的心肌炎会导致自主神经末梢受损。急性期过后会逐渐恢复。本研究展示了大鼠感染克氏锥虫期间心脏中胶质细胞源性神经营养因子(GDNF)和神经生长因子(NGF)的水平及其细胞来源。接种后第20天,即最大交感神经去神经支配的时间点,心房和心室的NGF水平(酶联免疫吸附测定)显著升高。酶联免疫吸附测定未显示心脏GDNF水平有显著升高。然而,免疫组织化学显示在第20天时,心房颗粒上抗GDNF金颗粒显著增加。光学显微镜显示心房心肌细胞和一些毛细血管中有更强的NGF免疫染色。原位杂交显示感染和未感染动物的心房和心室肌细胞中均有NGF和GDNF mRNA。仅在感染大鼠的内皮细胞中检测到NGF mRNA和蛋白。未发现浸润的单核细胞表达神经营养因子的证据。这是关于克氏锥虫感染期间神经营养因子表达的首次报道。我们的研究结果表明,NGF在能够损伤交感神经末梢的心肌炎后的再生现象中起重要作用,同时保留了神经终末前纤维和神经干。GDNF可能起次要或更短暂的作用。