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Journal of Neural Transmission

, Volume 122, Issue 7, pp 1055–1068 | Cite as

Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study

  • Pascal F. Durrenberger
  • Francesca S. Fernando
  • Samira N. Kashefi
  • Tim P. Bonnert
  • Danielle Seilhean
  • Brahim Nait-Oumesmar
  • Andrea Schmitt
  • Peter J. Gebicke-Haerter
  • Peter Falkai
  • Edna Grünblatt
  • Miklos Palkovits
  • Thomas Arzberger
  • Hans Kretzschmar
  • David T. Dexter
  • Richard Reynolds
Neurology and Preclinical Neurological Studies - Original Article

Abstract

Neurodegenerative diseases of the central nervous system are characterized by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity, iron accumulation and inflammation are observed in many neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome-wide gene expression data, using the Illumina HumanRef 8 Beadchip, for Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, Parkinson’s disease, and schizophrenia using an extensive cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of whole-genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease-specific changes, but more importantly to look for potential common molecular pathogenic mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all six diseases. However, 61 dysregulated genes were shared when comparing five and four diseases. The few genes highlighted by our direct gene comparison analysis hint toward common neuronal homeostatic, survival and synaptic plasticity pathways. In addition, we report changes to several inflammation-related genes in all diseases. This work is supportive of a general role of the innate immune system in the pathogenesis and/or response to neurodegeneration.

Keywords

Microarray Neurodegeneration Neuroinflammation Microglia Astrocytes Glia reactivity 

Notes

Acknowledgments

We would like to thank all the tissue donors and their families. Also, we are grateful to Veronique Sazdovitch and Kasztner Magdolna for technical assistance and Dr Isidro Ferrer for provision of tissues from the Institute of Neuropathology in Barcelona. This study was supported by the European Community under the Sixth Framework Programme (BrainNet Europe II, LSHM-CT-2004-503039). This paper reflects only the authors’ views, and the Community is not liable for any use that may be made of the information contained therein. The Multiple Sclerosis and Parkinson’s Disease Tissue Banks at Imperial were supported by the MS Society of Great Britain and the Parkinson’s UK, respectively.

Conflict of interest

None declared.

Supplementary material

702_2014_1293_MOESM1_ESM.pdf (45 kb)
Supplementary material 1 (PDF 45 kb)
702_2014_1293_MOESM2_ESM.pdf (232 kb)
Supplementary material 2 (PDF 231 kb)
702_2014_1293_MOESM3_ESM.pdf (106 kb)
Supplementary material 3 (PDF 105 kb)

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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Pascal F. Durrenberger
    • 1
  • Francesca S. Fernando
    • 1
  • Samira N. Kashefi
    • 1
  • Tim P. Bonnert
    • 2
  • Danielle Seilhean
    • 3
  • Brahim Nait-Oumesmar
    • 3
  • Andrea Schmitt
    • 4
    • 5
  • Peter J. Gebicke-Haerter
    • 6
    • 7
  • Peter Falkai
    • 4
  • Edna Grünblatt
    • 8
    • 9
  • Miklos Palkovits
    • 10
  • Thomas Arzberger
    • 11
    • 12
  • Hans Kretzschmar
    • 11
  • David T. Dexter
    • 1
  • Richard Reynolds
    • 1
  1. 1.Wolfson Neuroscience Laboratories, Division of Brain Sciences, Faculty of MedicineImperial College LondonLondonUK
  2. 2.QIAGEN Silicon ValleyRedwood CityUSA
  3. 3.AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie, Institut du Cerveau et de la Moelle épinière-ICMUniversité Pierre et Marie Curie-Sorbonne UniversitésParisFrance
  4. 4.Department of Psychiatry and PsychotherapyLudwig-Maximilians-UniversityMunichGermany
  5. 5.Laboratory of Neuroscience (LIM27), Institute of PsychiatryUniversity of Sao PauloSão PauloBrazil
  6. 6.Central Institute of Mental Health, Institute of Psychopharmacology, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  7. 7.Programme of Molecular and Clinical Pharmacology, ICBM, Medical FacultyUniversity of ChileSantiago 7Chile
  8. 8.University Clinics for Child and Adolescent Psychiatry (UCCAP)University of ZurichZurichSwitzerland
  9. 9.Neuroscience Center ZurichUniversity of Zurich and ETH ZurichZurichSwitzerland
  10. 10.Human Brain Tissue Bank and LaboratorySemmelweis UniversityBudapestHungary
  11. 11.Centre for Neuropathology and Prion ResearchLudwig-Maximilians-UniversityMunichGermany
  12. 12.Department of Psychiatry and PsychotherapyLudwig-Maximilians-UniversityMunichGermany

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