Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).

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...

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Autores principales:	Keiko Miwa, Jong-Kook Lee, Yoshiko Takagishi, Tobias Opthof, Xianming Fu, Masumi Hirabayashi, Kazuhiko Watabe, Yasuhiko Jimbo, Itsuo Kodama, Issei Komuro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e1e10d72205481caed266be9edb0950
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spelling	oai:doaj.org-article:9e1e10d72205481caed266be9edb09502021-11-18T07:38:54ZAxon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).1932-620310.1371/journal.pone.0065202https://doaj.org/article/9e1e10d72205481caed266be9edb09502013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23843937/?tool=EBIhttps://doaj.org/toc/1932-6203Molecular 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.Keiko MiwaJong-Kook LeeYoshiko TakagishiTobias OpthofXianming FuMasumi HirabayashiKazuhiko WatabeYasuhiko JimboItsuo KodamaIssei KomuroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e65202 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Keiko Miwa Jong-Kook Lee Yoshiko Takagishi Tobias Opthof Xianming Fu Masumi Hirabayashi Kazuhiko Watabe Yasuhiko Jimbo Itsuo Kodama Issei Komuro Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
description	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.
format	article
author	Keiko Miwa Jong-Kook Lee Yoshiko Takagishi Tobias Opthof Xianming Fu Masumi Hirabayashi Kazuhiko Watabe Yasuhiko Jimbo Itsuo Kodama Issei Komuro
author_facet	Keiko Miwa Jong-Kook Lee Yoshiko Takagishi Tobias Opthof Xianming Fu Masumi Hirabayashi Kazuhiko Watabe Yasuhiko Jimbo Itsuo Kodama Issei Komuro
author_sort	Keiko Miwa
title	Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
title_short	Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
title_full	Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
title_fullStr	Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
title_full_unstemmed	Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).
title_sort	axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (gdnf).
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9e1e10d72205481caed266be9edb0950
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Axon guidance of sympathetic neurons to cardiomyocytes by glial cell line-derived neurotrophic factor (GDNF).

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