Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human α-synuclein

Leonid Yavich; Mari Oksman; Heikki Tanila; Petri Kerokoski; Mikko Hiltunen; Thomas van Groen; Jukka Puoliväli; Pekka T. Männistö; Arturo García-Horsman; Ewen MacDonald; Konrad Beyreuther; Tobias Hartmann; Pekka Jäkälä

Neurobiology of Disease (Nov 2005)

Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human α-synuclein

Leonid Yavich,
Mari Oksman,
Heikki Tanila,
Petri Kerokoski,
Mikko Hiltunen,
Thomas van Groen,
Jukka Puoliväli,
Pekka T. Männistö,
Arturo García-Horsman,
Ewen MacDonald,
Konrad Beyreuther,
Tobias Hartmann,
Pekka Jäkälä

Affiliations

Leonid Yavich: Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland; Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland; Corresponding author. Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland. Fax: +358 17 162424.
Mari Oksman: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland
Heikki Tanila: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland; Department of Neurology, University Hospital of Kuopio, FIN-70211 Kuopio, Finland
Petri Kerokoski: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland
Mikko Hiltunen: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland
Thomas van Groen: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland
Jukka Puoliväli: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland
Pekka T. Männistö: Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland
Arturo García-Horsman: Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland
Ewen MacDonald: Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland
Konrad Beyreuther: Center for Molecular Biology (ZMBH), University of Heidelberg, D-69120, Germany
Tobias Hartmann: Center for Molecular Biology (ZMBH), University of Heidelberg, D-69120, Germany
Pekka Jäkälä: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland; Department of Neurology, University Hospital of Kuopio, FIN-70211 Kuopio, Finland

Journal volume & issue: Vol. 20, no. 2
pp. 303 – 313

Abstract

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We have generated a transgenic mouse line overexpressing mutated human A30P α-synuclein under the control of the prion-related protein promoter. Immunohistology revealed mutated human A30P α-synuclein protein in numerous brain areas, but no gross morphological changes, Lewy bodies, or loss of dopaminergic cell bodies. The transgenic mice displayed decreased locomotion, impaired motor coordination, and balance. In vivo voltammetry showed that A30P mice responded to longer stimulation of the ascending dopaminergic pathways with less dopamine release in striatum and had a slower rate of dopamine decline after repeated stimulations or after α-methyl-p-tyrosine-HCl treatment. However, dopamine re-uptake or transporter levels were similar in transgenic and control mice.Our data provide evidence that overexpression of mutated human A30P α-synuclein in mice leads to a reduced size of the dopamine storage pool. This is in agreement with the previously postulated involvement of α-synuclein in the turnover of transmitter vesicles and may explain the observed motor deficits in A30P mice.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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