title: Low levels of astroglial markers in Parkinson's disease: relationship to α-synuclein accumulation.
abstract: Although gliosis is a normal response to brain injury, reports on the extent of astrogliosis in the degenerating substantia nigra in Parkinson's disease (PD) are conflicting. It has also been recently suggested that accumulation of nigral α-synuclein in this disorder might suppress astrocyte activation which in turn could exacerbate the degenerative process. This study examined brain protein levels (intact protein, fragments, and aggregates, if any) of astroglial markers and their relationship to α-synuclein in PD and in the positive control parkinson-plus conditions multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Autopsied brain homogenates of patients with PD (n=10), MSA (n=11), PSP (n=11) and matched controls (n=10) were examined for the astroglial markers glial fibrillary acidic protein (GFAP), vimentin, and heat shock protein-27 (Hsp27) by quantitative immunoblotting. As expected, both MSA (putamen>substantia nigra>caudate>frontal cortex) and PSP (substantia nigra>caudate>putamen, frontal cortex) showed widespread but regionally specific pattern of increased immunoreactivity of the markers, in particular for the partially proteolyzed fragments (all three) and aggregates (GFAP). In contrast, immunoreactivity of the three markers was largely normal in PD in brain regions examined with the exception of trends for variably increased levels of cleaved vimentin in substantia nigra and frontal cortex. In patients with PD, GFAP levels in the substantia nigra correlated inversely with α-synuclein accumulation whereas the opposite was true for MSA. Our biochemical findings of generally normal protein levels of astroglial markers in substantia nigra of PD, and negative correlation with α-synuclein concentration, are consistent with some recent neuropathology reports of mild astroglial response and with the speculation that astrogliosis might be suppressed in this disorder by excessive α-synuclein accumulation. Should astrogliosis protect, to some extent, the degenerating substantia nigra from damage, therapeutics aimed at normalization of astrocyte reaction in PD could be helpful.
authors.affiliation: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: junchao.tong@camh.ca.
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
authors.affiliation: Division of Neuropathology, London Health Science Centre, University of Western Ontario, London, Ontario, Canada.
authors.forename: Lee-Cyn
authors.initials: LC
authors.lastname: Ang
authors.affiliation: Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Belinda
authors.initials: B
authors.lastname: Williams
authors.affiliation: Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, and Faculty of Medicine, University & Post Graduate University of Juntendo, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: The Drug Detection Agency, Auckland, New Zealand.
authors.forename: Paul
authors.initials: P
authors.lastname: Fitzmaurice
authors.affiliation: Centre for Movement Disorders, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Guttman
authors.affiliation: Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: Oleh
authors.initials: O
authors.lastname: Hornykiewicz
authors.affiliation: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
mesh_terms: D000368:Aged; D001253:Astrocytes / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002421:Caudate Nucleus / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005625:Frontal Lobe / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D019578:Multiple System Atrophy / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014746:Vimentin
keywords: Astrogliosis; Glial fibrillary acidic protein; Heat shock protein-27; Multiple system atrophy; Parkinson’s disease; Progressive supranuclear palsy; Quantitative Western blot; Substantia nigra; Vimentin; α-synuclein