title: Alpha-synuclein is upregulated in neurones in response to chronic oxidative stress and is associated with neuroprotection.
abstract: Chronic oxidative stress has been linked to the neurodegenerative changes characteristic of Parkinson's disease, particularly alpha-synuclein accumulation and aggregation. However, it remains contentious whether these alpha-synuclein changes are cytotoxic or neuroprotective. The current study utilised long-term primary neural culture techniques with antioxidant free media to study the cellular response to chronic oxidative stress. Cells maintained in antioxidant free media were exquisitely more vulnerable to acute exposure to hydrogen peroxide, yet exposure of up to 10 days in antioxidant free media did not lead to morphological alterations in neurones or glia. However, a subpopulation of neurones demonstrated a significant increase in the level of alpha-synuclein expressed within the cell body and at synaptic sites. This subset of neurones was also more resistant to apoptotic changes following exposure to antioxidant free media relative to other neurones. These data indicate that increased alpha-synuclein content is associated with neuroprotection from relatively low levels of oxidative stress.
authors.affiliation: NeuroRepair Group, University of Tasmania, Private Bag 29, Hobart, Tasmania 7001, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: Quilty
authors.forename: A E
authors.initials: AE
authors.lastname: King
authors.forename: W-P
authors.initials: WP
authors.lastname: Gai
authors.forename: D L
authors.initials: DL
authors.lastname: Pountney
authors.forename: A K
authors.initials: AK
authors.lastname: West
authors.forename: J C
authors.initials: JC
authors.lastname: Vickers
authors.forename: T C
authors.initials: TC
authors.lastname: Dickson
mesh_terms: D000818:Animals; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007150:Immunohistochemistry / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D050683:R-SNARE Proteins / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016877:Oxidants; D050683:R-SNARE Proteins; D051844:alpha-Synuclein; D004281:Docosahexaenoic Acids; D006861:Hydrogen Peroxide