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

Tofaris, George K., Reitbock, Pablo Gracia, Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799, Lambourne, Sarah L., O'Connell, Mark, Ghetti, Bernadino, Gossage, Helen, Emson, Piers C., Wilkinson, Lawrence Stephen ORCID: https://orcid.org/0000-0002-9337-6124, Goedert, Michel and Spillantini, Maria Grazia 2006. Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders. Journal of Neuroscience 26 (15) , pp. 3942-3950. 10.1523/JNEUROSCI.4965-05.2006

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	B Philosophy. Psychology. Religion > BF Psychology
Uncontrolled Keywords:	aggregation, behavior, tyrosine hydroxylase, fibril, dopamine, nigrostriatal, Parkinson, α-synuclein
Additional Information:	“Copyright of all material published in The Journal of Neuroscience remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.(http://creativecommons.org/licenses/)” See: http://www.jneurosci.org/site/misc/ifa_policies.xhtml
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Last Modified:	16 May 2023 02:30
URI:	https://orca.cardiff.ac.uk/id/eprint/3332

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