Cardiac NGF and GDNF expression during Trypanosoma cruzi infection in rats Patrícia Massara Martinelli a , Elizabeth Ribeiro da Silva Camargos a , Andréa Alves Azevedo a , Egler Chiari b , Gérard Morel c , Conceição Ribeiro da Silva Machado a, ⁎ a Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil b Department of Parasitology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil c UMR 5123, National Center of Scientific Research (CNRS), Claude Bernard-Lyon 1 University, Lyon, France Received 20 March 2006; received in revised form 8 May 2006; accepted 13 May 2006 Abstract 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. © 2006 Elsevier B.V. All rights reserved. Keywords: GDNF; NGF; Myocarditis; Trypanosoma cruzi infection; Sympathetic nerve regeneration 1. Introduction Neurotrophic factors are polypeptides able to influence survival, differentiation, maintenance and connectivity of different neuronal populations. Among the most studied neurotrophic factors are the neurotrophins that signal via the tyrosine kinase receptor family and the low-affinity receptor p75 NTR (reviewed by Ebadi et al., 1997; Boyd and Gordon, 2003). In the peripheral nervous system, the nerve growth factor (NGF), one of the neurotrophins, acts on sympathetic and neural crest-derived sensory neurons (Ebadi et al., 1997). There is a strong positive correlation between NGF protein or NGF mRNA levels and the density of sympathetic innervation assayed by noradrenaline content (Shelton and Reichardt, 1984). After destruction of sympathetic nerve terminals by 6-hydroxydopamine (6-OHDA) or blockade of axonal transport, NGF levels increase rapidly in sympathet- ically innervated organs (Korsching and Thoenen, 1985). The glial cell line derived neurotrophic factor (GDNF) family works through a unique multicomponent receptor complex (reviewed by Baloh et al., 2000). Besides its actions on the central nervous system, GDNF regulates the survival of sensory and autonomic (sympathetic, parasympathetic and enteric) neurons at different stages of their development (Matheson et al., 1997; Baloh et al., 2000). Accordingly, Autonomic Neuroscience: Basic and Clinical xx (2006) xxx – xxx MODEL 5 AUTNEU-00768; No of Pages 9 www.elsevier.com/locate/autneu ⁎ Corresponding author. Tel.: +55 31 34992796; fax: +55 31 34992810. E-mail address: cmachado@icb.ufmg.br (C.R.S. Machado). 1566-0702/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.autneu.2006.05.004 ARTICLE IN PRESS