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

Neurobiology of Disease

Heikki Tanila¹  Thomas van Groen²  Mari Oksman³  Mikko Hiltunen⁴  Arturo García-Horsman⁴  Jukka Puoliväli⁴  Petri Kerokoski⁴  Ewen MacDonald⁴  Pekka T. Männistö⁴  Tobias Hartmann⁵  Konrad Beyreuther⁵  Pekka Jäkälä⁵  Leonid Yavich⁵ 

[1] Corresponding author. Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland. Fax: [phone].;Department of Neurology, University Hospital of Kuopio, FIN-70211 Kuopio, Finland;Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland;Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland;Department of Pharmacology and Toxicology, University of Kuopio, FIN-70211 Kuopio, Finland;

关键词: Parkinson's disease;    Alpha-synuclein;    Transgenic mice;    Striatum;    Dopamine;    In vivo voltammetry;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown