Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human α-synuclein(1- 120): Implications for lewy body disorders

George K. Tofaris, Pablo Garcia Reitböck, Trevor Humby, Sarah L. Lambourne, Mark O'Connell, Bernardino Ghetti, Helen Gossage, Piers C. Emson, Lawrence S. Wilkinson, Michel Goedert, Maria Grazia Spillantini

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

Dysfunction of the 140 aa protein α-synuclein plays a central role in Lewy body disorders, including Parkinson's disease, as well as in multiple system atrophy. Here, we show that the expression of truncated human α-synuclein(1-120), driven by the rat tyrosine hydroxylase promoter on a mouse α-synuclein null background, leads to the formation of pathological inclusions in the substantia nigra and olfactory bulb and to a reduction in striatal dopamine levels. At the behavioral level, the transgenic mice showed a progressive reduction in spontaneous locomotion and an increased response to amphetamine. These findings suggest that the C-terminal of α-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders and multiple system atrophy.

Original languageEnglish (US)
Pages (from-to)3942-3950
Number of pages9
JournalJournal of Neuroscience
Volume26
Issue number15
DOIs
StatePublished - 2006

Keywords

  • α-synuclein
  • Aggregation
  • Behavior
  • Dopamine
  • Fibril
  • Nigrostriatal
  • Parkinson
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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    Tofaris, G. K., Reitböck, P. G., Humby, T., Lambourne, S. L., O'Connell, M., Ghetti, B., Gossage, H., Emson, P. C., Wilkinson, L. S., Goedert, M., & Spillantini, M. G. (2006). Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human α-synuclein(1- 120): Implications for lewy body disorders. Journal of Neuroscience, 26(15), 3942-3950. https://doi.org/10.1523/JNEUROSCI.4965-05.2006