Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

被引：7
作者：
Miwa, Keiko
Lee, Jong-Kook [1 ]
Takagishi, Yoshiko [3 ]
Opthof, Tobias [2 ,4 ]
Fu, Xianming [5 ]
Kodama, Itsuo
机构：
[1] Nagoya Univ, Dept Cardiovasc Res, Environm Med Res Inst, Chikusa Ku, Nagoya, Aichi 4648601, Japan
[2] Univ Amsterdam, Acad Med Ctr, Ctr Heart Failure Res, Expt Cardiol Grp, NL-1105 AZ Amsterdam, Netherlands
[3] Nagoya Univ, Dept Genet, Environm Med Res Inst, Nagoya, Aichi 4648601, Japan
[4] Univ Med Ctr Utrecht, Dept Med Physiol, Utrecht, Netherlands
[5] Nagoya Univ, Dept Cardiovasc Surg, Grad Sch Med, Nagoya, Aichi 4648601, Japan
来源：
BIOMEDICAL RESEARCH-TOKYO | 2010年 / 31卷 / 06期
关键词：
NERVOUS-SYSTEM; EXPRESSION; INNERVATION; NEURONS; ARTEMIN; MICE; TRKA; NGF;
D O I：
10.2220/biomedres.31.353
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and a-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.
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页码：353 / 361
页数：9
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