title: 6-Hydroxydopamine induces distinct alterations in GDF5 and GDNF mRNA expression in the rat nigrostriatal system in vivo.
abstract: Growth/differentiation factor (GDF)5 and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that promote the survival of midbrain dopaminergic neurons in vitro and in vivo. Both factors have potent neurotrophic and neuroprotective effects in rat models of Parkinson's disease (PD) and represent promising new therapies for PD. The aim of this study was to investigate the expression of GDF5, GDNF and their receptors in the nigrostriatal dopaminergic system in rat models of PD. It found that endogenous GDF5, GDNF and their receptors are differentially expressed in two 6-hydroxydopamine lesion models of PD. In both striatal and medial forebrain bundle (MFB) lesion models, striatal levels of GDF5 mRNA increased at 10 days post-lesion, while GDNF mRNA levels in the nigrostriatal system decreased after 10 and 28 days. Midbrain mRNA levels for both GDF5 receptors transiently increased after striatal lesion, whereas those of two GDNF receptors decreased at later time-points in both models. Despite the fact that exogenous GDF5 and GDNF have comparable effects on dopaminergic neurons in vitro and in vivo, their endogenous responses to neurotoxic injury are different. This highlights the importance of studying neurotrophic factor expression at distinct disease stages and in various animal models of PD.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Aisling M
authors.initials: AM
authors.lastname: Gavin
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Sinéad
authors.initials: S
authors.lastname: Walsh
authors.affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Wyatt
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: g.okeeffe@ucc.ie.
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland. Electronic address: a.sullivan@ucc.ie.
authors.forename: Aideen M
authors.initials: AM
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism; D055428:Growth Differentiation Factor 5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D055428:Growth Differentiation Factor 5; D012333:RNA, Messenger; D016627:Oxidopamine; D051096:Proto-Oncogene Proteins c-ret; C495001:Ret protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II
keywords: 6-Hydroxydopamine; Dopaminergic; GDF5; GDNF; Parkinson's disease