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Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons
Author(s) -
Wanigasekara Yewlan,
Keast Janet R.
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04260.x
Subject(s) - neurturin , neurotrophic factors , neuroscience , neurotrophin , biology , neurite , creb , microbiology and biotechnology , axotomy , gdnf family of ligands , superior cervical ganglion , endocrinology , medicine , glial cell line derived neurotrophic factor , central nervous system , transcription factor , receptor , gene , in vitro , biochemistry
Neurturin (NTN) is an important neurotrophic factor for parasympathetic neurons; however, no studies to date have investigated the signalling mechanisms downstream of GFRα2 and Ret activation underlying this neurotrophic support. This is particularly important for pelvic parasympathetic neurons, which are prone to injury during surgical procedures such as prostatectomy, and where there are no current therapies for axonal regeneration. To address this issue we have cultured dissociated adult rat pelvic ganglion neurons and also examined the structural changes in pelvic ganglion neurons after axotomy. Axotomised penile neurons deprived of target‐derived support had smaller somata than intact neurons. Studies of cultured adult pelvic ganglion neurons also demonstrated that NTN stimulated soma growth. Further experiments showed that NTN reduced the up‐regulation of tyrosine hydroxylase expression in cultured pelvic parasympathetic neurons. NTN stimulated the extension of neurites in cultured parasympathetic, but not sympathetic, pelvic ganglion neurons. Inhibition of phosphatidylinositol 3‐kinase prevented initiation of neurite outgrowth, whereas inhibition of the mitogen‐activated protein kinase and the Src family kinase pathways disrupted NTN‐stimulated microtubule assembly. Surprisingly, NTN did not activate the transcription factor cAMP‐response element binding protein (CREB), which is typically involved in neurotrophic signalling in sympathetic neurons. This is the first study to identify signalling pathways activated by NTN in adult parasympathetic neurons. Our results may lead to a better understanding of regenerative mechanisms in parasympathetic neurons, especially for those innervating urogenital organs. Our results also indicate that neurotrophic signalling in parasympathetic neurons is different from that in other types of peripheral neurons.