Direct detection of alpha synuclein oligomers in vivo

Hemi Dimant, Suneil K. Kalia, Lorraine V. Kalia, Liya N. Zhu, Laura Kibuuka, Darius Ebrahimi-Fakhari, Nikolaus R. McFarland, Zhanyun Fan, Bradley T. Hyman, Pamela J. McLean

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background: Rat models of Parkinson's disease are widely used to elucidate the mechanisms underlying disease etiology or to investigate therapeutic approaches. Models were developed using toxins such as MPTP or 6-OHDA to specifically target dopaminergic neurons resulting in acute neuronal loss in the substantia nigra or by using viral vectors to induce the specific and gradual expression of alpha synuclein in the substantia nigra. The detection of alpha- synuclein oligomers, the presumed toxic species, in these models and others has been possible using only indirect biochemical approaches to date. Here we coinjected AAVs encoding alpha-synuclein fused to the N- or C-terminal half of VenusYFP in rat substantia nigra pars compacta and describe for the first time a novel viral vector rodent model with the unique ability to directly detect and track alpha synuclein oligomers ex vivo and in vivo. Results: Viral coinjection resulted in widespread VenusYFP signal within the nigrostriatal pathway, including cell bodies in the substantia nigra and synaptic accumulation in striatal terminals, suggestive of in vivo alpha-synuclein oligomers formation. Transduced rats showed alpha-synuclein induced dopaminergic neuron loss in the substantia nigra, the appearance of dystrophic neurites, and gliosis in the striatum. Moreover, we have applied in vivo imaging techniques in the living mouse to directly image alpha-synuclein oligomers in the cortex. Conclusion: We have developed a unique animal model that provides a tool for the Parkinson's disease research community with which to directly detect alpha- synuclein oligomers in vivo and screen therapeutic approaches targeting alpha-synuclein oligomers.

Original languageEnglish (US)
Article number6
JournalActa Neuropathologica Communications
Volume2
Issue number1
DOIs
StatePublished - Jan 27 2014

Keywords

  • Alpha synuclein
  • Animal model
  • Live imaging
  • Oligomers
  • Parkinson's disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Direct detection of alpha synuclein oligomers in vivo'. Together they form a unique fingerprint.

  • Cite this

    Dimant, H., Kalia, S. K., Kalia, L. V., Zhu, L. N., Kibuuka, L., Ebrahimi-Fakhari, D., McFarland, N. R., Fan, Z., Hyman, B. T., & McLean, P. J. (2014). Direct detection of alpha synuclein oligomers in vivo. Acta Neuropathologica Communications, 2(1), [6]. https://doi.org/10.1186/2051-5960-1-6