Skip to main content
SpringerLink
Log in

Absence of α-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

α-Synuclein is a major constituent of glial cytoplasmic inclusions (GCIs), which are pathognomic for multiple system atrophy (MSA). We have previously demonstrated that in normal human brain, α-synuclein mRNA has a restricted pattern of neuronal expression and no apparent glial expression. The current study used double-label in situ hybridization to determine if α-synuclein mRNA is expressed by oligodendroglia of MSA cases. Analysis of MSA brain tissue revealed depletion of regional signal for this transcript in many brain areas due to extensive neurodegeneration. Cellular analysis of oligodendroglia in crus cerebri, a GCI-rich region ventral to substantia nigra, revealed an absence of α-synuclein mRNA signal in control and MSA cases. However, an abundance of this transcript was detected in melanin-containing neurons of substantia nigra. Therefore, oligodendroglia do not express α-synuclein mRNA in control and MSA cases suggesting that involvement of α-synuclein in GCI pathology of MSA is due to its ectopic presence in oligodendroglia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • K Arima K Ueda N Sunohara K Arakawa S Hirai M Nakamura H Tonozuka-Uehara M Kawai (1998) ArticleTitleNACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol (Berl) 96 439–444 Occurrence Handle1:CAS:528:DyaK1cXmtFegtLc%3D

    CAS  Google Scholar 

  • R Borghi R Marchese A Negro L Marinelli G Forloni D Zaccheo G Abbruzzese M Tabaton (2000) ArticleTitleFull length alpha-synuclein is present in cerebrospinal fluid from Parkinson’s disease and normal subjects. Neurosci Lett 287 65–67 Occurrence Handle10.1016/S0304-3940(00)01153-8 Occurrence Handle10841992 Occurrence Handle1:CAS:528:DC%2BD3cXjslOqs7k%3D

    Article  PubMed  CAS  Google Scholar 

  • TJ Counihan B Landwehrmeyer DG Standaert CM Kosinski CR Scherzer LP Daggett G Velicelebi AB Young JB Penney (1998) ArticleTitleExpression of N-methyl-D-aspartate receptor subunit mRNA in the human brain: mesencephalic dopaminergic neurons. J Comp Neurol 390 91–101 Occurrence Handle10.1002/(SICI)1096-9861(19980105)390:1<91::AID-CNE8>3.0.CO;2-L Occurrence Handle9456178 Occurrence Handle1:CAS:528:DyaK1cXhvVynsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • OM El-Agnaf SA Salem KE Paleologou LJ Cooper NJ Fullwood MJ Gibson MD Curran JA Court DM Mann S Ikeda MR Cookson J Hardy D Allsop (2003) ArticleTitleAlpha-synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. Faseb J 17 1945–1947 Occurrence Handle14519670 Occurrence Handle1:CAS:528:DC%2BD3sXot1Kit7Y%3D

    PubMed  CAS  Google Scholar 

  • M Farrer J Kachergus L Forno S Lincoln DS Wang M Hulihan D Maraganore K Gwinn-Hardy Z Wszolek D Dickson JW Langston (2004) ArticleTitleComparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol 55 174–179 Occurrence Handle10.1002/ana.10846 Occurrence Handle14755720 Occurrence Handle1:CAS:528:DC%2BD2cXhs1Sgtbo%3D

    Article  PubMed  CAS  Google Scholar 

  • H Fujiwara M Hasegawa N Dohmae A Kawashima E Masliah MS Goldberg J Shen K Takio T Iwatsubo (2002) ArticleTitlealpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4 160–164 Occurrence Handle10.1038/ncb841 Occurrence Handle11813001 Occurrence Handle1:CAS:528:DC%2BD38XhsVKnur4%3D

    Article  PubMed  CAS  Google Scholar 

  • S Gilman PA Low N Quinn A Albanese Y Ben-Shlomo CJ Fowler H Kaufmann T Klockgether AE Lang PL Lantos I Litvan CJ Mathias E Oliver D Robertson I Schatz GK Wenning (1999) ArticleTitleConsensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163 94–98 Occurrence Handle10.1016/S0022-510X(98)00304-9 Occurrence Handle10223419 Occurrence Handle1:STN:280:DyaK1M3jsl2gsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • K Gwinn-Hardy ND Mehta M Farrer D Maraganore M Muenter SH Yen J Hardy DW Dickson (2000) ArticleTitleDistinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. Acta Neuropathol (Berl) 99 663–672 Occurrence Handle1:CAS:528:DC%2BD3cXjtVWrsbg%3D

    CAS  Google Scholar 

  • Y Honjyo Y Kawamoto S Nakamura S Nakano I Akiguchi (2001) ArticleTitleP39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple system atrophy. Acta Neuropathol (Berl) 101 190–194 Occurrence Handle1:CAS:528:DC%2BD3MXht1ejs74%3D

    CAS  Google Scholar 

  • MC Irizarry TW Kim M McNamara RE Tanzi JM George DF Clayton BT Hyman (1996) ArticleTitleCharacterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system. J Neuropathol Exp Neurol 55 889–895 Occurrence Handle8759778 Occurrence Handle1:CAS:528:DyaK28XlsVSntr8%3D

    PubMed  CAS  Google Scholar 

  • A Iwai E Masliah M Yoshimoto N Ge L Flanagan HA de Silva A Kittel T Saitoh (1995) ArticleTitleThe precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron 14 467–475 Occurrence Handle10.1016/0896-6273(95)90302-X Occurrence Handle7857654 Occurrence Handle1:CAS:528:DyaK2MXjvFejsLY%3D

    Article  PubMed  CAS  Google Scholar 

  • KA Jellinger K Seppi GK Wenning (2005) ArticleTitleGrading of neuropathology in multiple system atrophy: proposal for a novel scale. Mov Disord 20 IssueID[Suppl 12] S29–S36 Occurrence Handle16092088

    PubMed  Google Scholar 

  • PJ Kahle M Neumann L Ozmen V Muller H Jacobsen W Spooren B Fuss B Mallon WB Macklin H Fujiwara M Hasegawa T Iwatsubo HA Kretzschmar C Haass (2002) ArticleTitleHyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 3 583–588 Occurrence Handle10.1093/embo-reports/kvf109 Occurrence Handle12034752 Occurrence Handle1:CAS:528:DC%2BD38XltVykt74%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Kerner DG Standaert JB Penney AB Young GB Landwehrmeyer (1998) ArticleTitleSimultaneous isotopic and nonisotopic in situ hybridization histochemistry with cRNA probes. Brain Res Protocols 3 22–32 Occurrence Handle10.1016/S1385-299X(98)00017-8 Occurrence Handle1:CAS:528:DyaK1cXnsVChur0%3D

    Article  CAS  Google Scholar 

  • PL Lantos (1998) ArticleTitleThe definition of multiple system atrophy: a review of recent developments. J Neuropathol Exp Neurol 57 1099–1111 Occurrence Handle9862632 Occurrence Handle1:STN:280:DyaK1M%2FnslClug%3D%3D

    PubMed  CAS  Google Scholar 

  • L Maroteaux JT Campanelli RH Scheller (1988) ArticleTitleSynuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8 2804–2815 Occurrence Handle3411354 Occurrence Handle1:CAS:528:DyaL1MXhsVyqsbY%3D

    PubMed  CAS  Google Scholar 

  • DW Miller MR Cookson DW Dickson (2004a) ArticleTitleGlial cell inclusions and the pathogenesis of neurodegenerative diseases. Neuron Glia Biol 1 13–21 Occurrence Handle10.1017/S1740925X04000043

    Article  Google Scholar 

  • DW Miller SM Hague J Clarimon M Baptista K Gwinn-Hardy MR Cookson AB Singleton (2004b) ArticleTitleAlpha-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 62 1835–1838 Occurrence Handle1:CAS:528:DC%2BD2cXjs1yltbs%3D

    CAS  Google Scholar 

  • F Mori K Tanji M Yoshimoto H Takahashi K Wakabayashi (2002) ArticleTitleDemonstration of alpha-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol 176 98–104 Occurrence Handle10.1006/exnr.2002.7929 Occurrence Handle12093086 Occurrence Handle1:CAS:528:DC%2BD38XkvFKrsrk%3D

    Article  PubMed  CAS  Google Scholar 

  • S Nakamura Y Kawamoto S Nakano I Akiguchi J Kimura (1998) ArticleTitleCyclin-dependent kinase 5 and mitogen-activated protein kinase in glial cytoplasmic inclusions in multiple system atrophy. J Neuropathol Exp Neurol 57 690–698 Occurrence Handle9690673 Occurrence Handle1:CAS:528:DyaK1cXlt1alsLo%3D

    PubMed  CAS  Google Scholar 

  • S Nakamura Y Kawamoto S Nakano I Akiguchi (2000) ArticleTitleExpression of the endocytosis regulatory proteins Rab5 and Rabaptin-5 in glial cytoplasmic inclusions from brains with multiple system atrophy. Clin Neuropathol 19 51–56 Occurrence Handle10749284 Occurrence Handle1:STN:280:DC%2BD3c3htVymtw%3D%3D

    PubMed  CAS  Google Scholar 

  • T Ozawa K Okuizumi T Ikeuchi K Wakabayashi H Takahashi S Tsuji (2001) ArticleTitleAnalysis of the expression level of alpha-synuclein mRNA using postmortem brain samples from pathologically confirmed cases of multiple system atrophy. Acta Neuropathol (Berl) 102 188–190 Occurrence Handle1:CAS:528:DC%2BD3MXlslGksLk%3D

    CAS  Google Scholar 

  • MI Papp JE Kahn PL Lantos (1989) ArticleTitleGlial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94 79–100 Occurrence Handle10.1016/0022-510X(89)90219-0 Occurrence Handle2559165 Occurrence Handle1:STN:280:By%2BC3s3nvVI%3D

    Article  PubMed  CAS  Google Scholar 

  • YS Piao S Hayashi M Hasegawa K Wakabayashi M Yamada M Yoshimoto A Ishikawa T Iwatsubo H Takahashi (2001) ArticleTitleCo-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration. Acta Neuropathol (Berl) 101 285–293 Occurrence Handle1:STN:280:DC%2BD3MvotlGrsQ%3D%3D

    CAS  Google Scholar 

  • C Richter-Landsberg M Gorath JQ Trojanowski VM Lee (2000) ArticleTitlealpha-synuclein is developmentally expressed in cultured rat brain oligodendrocytes. J Neurosci Res 62 9–14 Occurrence Handle10.1002/1097-4547(20001001)62:1<9::AID-JNR2>3.0.CO;2-U Occurrence Handle11002283 Occurrence Handle1:CAS:528:DC%2BD3cXnsVSgtLY%3D

    Article  PubMed  CAS  Google Scholar 

  • AB Singleton M Farrer J Johnson A Singleton S Hague J Kachergus M Hulihan T Peuralinna A Dutra R Nussbaum S Lincoln A Crawley M Hanson D Maraganore C Adler MR Cookson M Muenter M Baptista D Miller J Blancato J Hardy K Gwinn-Hardy (2003) ArticleTitlealpha-Synuclein locus triplication causes Parkinson’s disease. Science 302 841 Occurrence Handle10.1126/science.1090278 Occurrence Handle14593171 Occurrence Handle1:CAS:528:DC%2BD3sXoslehsbc%3D

    Article  PubMed  CAS  Google Scholar 

  • SM Solano DW Miller SJ Augood AB Young JB Penney SuffixJr (2000) ArticleTitleExpression of alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 mRNA in human brain: genes associated with familial Parkinson’s disease. Ann Neurol 47 201–210 Occurrence Handle10.1002/1531-8249(200002)47:2<201::AID-ANA10>3.0.CO;2-F Occurrence Handle10665491 Occurrence Handle1:CAS:528:DC%2BD3cXhtV2mtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • MG Spillantini RA Crowther R Jakes NJ Cairns PL Lantos M Goedert (1998) ArticleTitleFilamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251 205–208 Occurrence Handle9726379 Occurrence Handle1:STN:280:DyaK1czpt12rsg%3D%3D

    PubMed  CAS  Google Scholar 

  • JY Sung J Kim SR Paik JH Park YS Ahn KC Chung (2001) ArticleTitleInduction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem 276 27441–27448 Occurrence Handle11316809 Occurrence Handle1:CAS:528:DC%2BD3MXlsV2is7s%3D

    PubMed  CAS  Google Scholar 

  • K Wakabayashi M Yoshimoto S Tsuji H Takahashi (1998) ArticleTitleAlpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249 180–182 Occurrence Handle10.1016/S0304-3940(98)00407-8 Occurrence Handle9682846 Occurrence Handle1:CAS:528:DyaK1cXjvVWisLg%3D

    Article  PubMed  CAS  Google Scholar 

  • GK Wenning F Tison Y Ben Shlomo SE Daniel NP Quinn (1997) ArticleTitleMultiple system atrophy: a review of 203 pathologically proven cases. Mov Disord 12 133–147 Occurrence Handle9087971 Occurrence Handle1:STN:280:ByiB2c3pvFU%3D

    PubMed  CAS  Google Scholar 

  • I Yazawa BI Giasson R Sasaki B Zhang S Joyce K Uryu JQ Trojanowski VM Lee (2005) ArticleTitleMouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 45 847–859 Occurrence Handle10.1016/j.neuron.2005.01.032 Occurrence Handle15797547 Occurrence Handle1:CAS:528:DC%2BD2MXjt1Oitb4%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, NIA, Bethesda, MD, USA

    D. W. Miller

  2. Mass General Institute for Neurodegenerative Disease, Charlestown, MA, USA

    J. M. Johnson, S. M. Solano, Z. R. Hollingsworth, D. G. Standaert & A. B. Young

Authors
  1. D. W. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. M. Solano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Z. R. Hollingsworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. G. Standaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. B. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miller, D., Johnson, J., Solano, S. et al. Absence of α-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia. J Neural Transm 112, 1613–1624 (2005). https://doi.org/10.1007/s00702-005-0378-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0378-1

Search

Navigation