Rat heart GDNF: effect of chemical sympathectomy
Rat heart GDNF: effect of chemical sympathectomy
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DOI：
10.1007/s00418-002-0452-9
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发表时间：
2002-10-01
影响因子：
2.3
通讯作者：
Machado, CRS
中科院分区：
文献类型：
--
作者：
Martinelli, PM;Camargos, ERS;Machado, CRS
发育研究表明GDNF在运动神经元、自主神经元和感觉神经元的存活中起作用。然而，没有研究试图证明其参与自主神经再生。在这项工作中，6-羟基多巴胺化学交感神经切除术提供了模型，用于评估心脏GDNF表达在去神经和轴突再生。乙醛酸为基础的组织化学技术评价去甲肾上腺素能神经支配。ELISA测定浓缩心脏匀浆后的GDNF水平。光镜和超微结构原位杂交及免疫细胞化学法鉴定表达GDNF mRNA和蛋白的细胞。在对照组大鼠中，GDNF心脏水平在37日龄的动物中显著高于60日龄的动物。在交感神经切断的大鼠中，GDNF心脏水平在交感神经切除术后7天显著升高，并在第30天降至对照水平。GDNF mRNA在正常和交感神经切断大鼠心房和心室肌细胞中均有表达。GDNF免疫反应发生在心房颗粒和定量分析的电子显微镜证实ELISA获得的数据。心室肌细胞内金颗粒分布稀疏。这些发现构成了GDNF合成心肌细胞的第一个证据，并假定心脏交感神经去神经后不久，这个因素的作用，可能在神经再生。在心房肌细胞中，GDNF可能通过调节途径分泌。
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 immunocytochernistry 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 sympathectornized 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 sympathectornized 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.