Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
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DOI：
10.1371/journal.pone.0065202
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Komuro I
中科院分区：
文献类型：
--
作者：
Miwa K;Lee JK;Takagishi Y;Opthof T;Fu X;Hirabayashi M;Watabe K;Jimbo Y;Kodama I;Komuro I
心脏自主神经支配的分子信号是一个尚未解决的问题。在这里，我们证明了神经胶质细胞系来源的神经营养因子（GDNF）在体外和体内促进心脏交感神经支配。体外近距离培养从新生大鼠脑室和颈上神经节分离的心室肌细胞（vm）和交感神经元（SNs）。然后，评估GDNF （10 ng/ml）或神经生长因子（50 ng/ml）对SNs和vm之间形态和功能耦合的反应。结果，与未添加神经营养因子的对照组相比，添加GDNF后vm表面的神经丝m阳性轴突和突触素i阳性面积分别显著增加了9倍和25倍。在GDNF的作用下，分别用尼古丁和去甲肾上腺素刺激β1-肾上腺素能受体（BAR）突触前和突触后，可提高与SNs共培养的vm的自发搏动率。腺病毒载体转染过表达GDNF的虚拟机比模拟转染的虚拟机吸引更多的轴突。在体内，腺病毒介导的GDNF过表达也显著增强了成年大鼠心脏冷冻损伤后轴突向失神经心肌的生长。GDNF是心室肌细胞交感神经支配的有效化学引诱剂，是病变心脏功能调控的一个有希望的分子靶点。
Molecular signaling of cardiac autonomic innervation is an unresolved issue. Here, we show that glial cell line-derived neurotrophic factor (GDNF) promotes cardiac sympathetic innervation in vitro and in vivo. In vitro, ventricular myocytes (VMs) and sympathetic neurons (SNs) isolated from neonatal rat ventricles and superior cervical ganglia were cultured at a close distance. Then, morphological and functional coupling between SNs and VMs was assessed in response to GDNF (10 ng/ml) or nerve growth factor (50 ng/ml). As a result, fractions of neurofilament-M-positive axons and synapsin-I-positive area over the surface of VMs were markedly increased with GDNF by 9-fold and 25-fold, respectively, compared to control without neurotrophic factors. Pre- and post-synaptic stimulation of β1-adrenergic receptors (BAR) with nicotine and noradrenaline, respectively, resulted in an increase of the spontaneous beating rate of VMs co-cultured with SNs in the presence of GDNF. GDNF overexpressing VMs by adenovirus vector (AdGDNF-VMs) attracted more axons from SNs compared with mock-transfected VMs. In vivo, axon outgrowth toward the denervated myocardium in adult rat hearts after cryoinjury was also enhanced significantly by adenovirus-mediated GDNF overexpression. GDNF acts as a potent chemoattractant for sympathetic innervation of ventricular myocytes, and is a promising molecular target for regulation of cardiac function in diseased hearts.
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影响因子：
20.1
作者：
Zhou, SM;Chen, LS;Chen, PS
通讯作者：
Chen, PS
影响因子：
2.7
作者：
Martinelli, Patricia Massara;da Silva Camargos, Elizabeth Ribeiro;da Silva Machado, Conceicao Ribeiro
通讯作者：
da Silva Machado, Conceicao Ribeiro
影响因子：
2.3
作者：
Martinelli, PM;Camargos, ERS;Machado, CRS
通讯作者：
Machado, CRS
DOI：
10.1006/bbrc.2001.5452
发表时间：
2001-08-31
影响因子：
3.1
作者：
Hakamata, Y;Tahara, K;Kobayashi, E
通讯作者：
Kobayashi, E
影响因子：
5.5
作者：
Oh, Yong-Seog;Jong, Ambrose Y.;Chen, Lan S.
通讯作者：
Chen, Lan S.