title: Increased tyrosine hydroxylase expression accompanied by glial changes within the non-lesioned hemisphere in the 6-hydroxydopamine model of Parkinson's disease.
abstract: OBJECTIVE
  Parkinson's disease (PD) is characterized by striatal synaptic deafferentation followed by dopaminergic cell death in the substantia nigra pars compacta. Not only degenerative, but also regenerative, compensatory changes at distant sites of the primary lesion may occur in PD. The aim of the study was to analyze the temporal pattern of axonal and glial responses over a time course of six weeks post-lesioning.
  
  
  METHODS
  For this aim, 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle and both lesioned and non-lesioned striata were analyzed.
  
  
  RESULTS
  We detected increased tyrosine hydroxylase (TH) immunoreactivity within the non-lesioned striatum six weeks after injection indicative either of increased TH expression or compensatory neuritic changes. An increased number of microglial cells was present in both lesioned and unlesioned striata. There was no obvious change in microglial phenotype or in pro-inflammatory cytokine gene expression within the striatum without any apparent switch into a pro-inflammatory phenotype. No changes were observed in the number of mature oligodendrocytes.
  
  
  CONCLUSIONS
  This temporal pattern shows, that the non-lesioned striatum undergoes profound changes, involving increased TH expression accompanied by a glial response. A better understanding of this complex interplay of neuronal as well as glial components not only within the lesioned, but also non-lesioned striatum may help to restore local neural circuits in PD.
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Johannes C M
authors.initials: JC
authors.lastname: Schlachetzki
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany Department of Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Marxreiter
authors.affiliation: Department of Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany IZKF Junior Research Group III, Nikolaus-Fiebiger-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Regensburger
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kulinich
authors.affiliation: IZKF Junior Research Group III, Nikolaus-Fiebiger-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D065842:Pars Compacta / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-hydroxydopamine; Parkinson's disease; astrocyte; axonal degeneration; microglia; oligodendrocyte