Implanted Reuptake-deficient or Wild-type Dopaminergic Neurons Improve ON L-dopa Dyskinesias Without OFF-dyskinesias in a Rat Model of Parkinson's Disease

Implanted Reuptake-deficient or Wild-type Dopaminergic Neurons Improve ON L-dopa Dyskinesias Without OFF-dyskinesias in a Rat Model of Parkinson's Disease

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Implanted Reuptake-deficient or Wild-type Dopaminergic Neurons Improve ON L-dopa Dyskinesias Without OFF-dyskinesias in a Rat Model of Parkinson's Disease

dc.contributor.author	Reske-Nielsen, C.
dc.contributor.author	Patterson, M.
dc.contributor.author	Sotnikova, T. D.
dc.contributor.author	Caron, M. G.
dc.contributor.author	Gainetdinov, R. R.
dc.contributor.author	Vinuela, Angel
dc.contributor.author	Hallett, Penelope Jane
dc.contributor.author	Isacson, Ole Stefan
dc.date.accessioned	2012-03-29T18:09:55Z
dc.date.issued	2008
dc.identifier.citation	Vinuela, A., P. J. Hallett, C. Reske-Nielsen, M. Patterson, T. D. Sotnikova, M. G. Caron, R. R. Gainetdinov, and O. Isacson. 2008. Implanted reuptake-deficient or wild-type dopaminergic neurons improve ON L-dopa dyskinesias without OFF-dyskinesias in a rat model of Parkinson's disease. Brain 131(12): 3361-3379.	en_US
dc.identifier.issn	0006-8950	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:8462359
dc.description.abstract	OFF-L-dopa dyskinesias have been a surprising side-effect of intrastriatal foetal ventral mesencephalic transplantation in patients with Parkinson's disease. It has been proposed that excessive and unregulated dopaminergic stimulation of host post-synaptic striatal neurons by the grafts could be responsible for these dyskinesias. To address this issue we transplanted foetal dopaminergic neurons from mice lacking the dopamine transporter (DATKO) or from wild-type mice, into a rat model of Parkinson's disease and L-dopa-induced dyskinesias. Both wild-type and DATKO grafts reinnervated the host striatum to a similar extent, but DATKO grafts produced a greater and more diffuse increase in extra-cellular striatal dopamine levels. Interestingly, grafts containing wild-type dopaminergic neurons improved parkinsonian signs to a similar extent as DATKO grafts, but provided a more complete reduction of L-dopa induced dyskinesias. Neither DATKO nor wild-type grafts induced OFF-L-dopa dyskinesias. Behavioural and receptor autoradiography analyses demonstrated that DATKO grafts induced a greater normalization of striatal dopaminergic receptor supersensitivity than wild-type grafts. Both graft types induced a similar downregulation and normalization of PEnk and fosb/Δfosb in striatal neurons. In summary, DATKO grafts causing high and diffuse extra-cellular dompamine levels do not per se alter graft-induced recovery or produce OFF-L-dopa dyskinesias. Wild-type dopaminergic neurons appear to be the most effective neuronal type to restore function and reduce L-dopa-induced dyskinesias.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Oxford University Press	en_US
dc.relation.isversionof	doi:10.1093/brain/awn192	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639209/pdf/	en_US
dash.license	LAA
dc.subject	Parkinson’s disease	en_US
dc.subject	transplantation	en_US
dc.subject	dyskinesia	en_US
dc.subject	dopamine	en_US
dc.subject	synapse	en_US
dc.title	Implanted Reuptake-deficient or Wild-type Dopaminergic Neurons Improve ON L-dopa Dyskinesias Without OFF-dyskinesias in a Rat Model of Parkinson's Disease	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	Brain	en_US
dash.depositing.author	Vinuela, Angel
dc.date.available	2012-03-29T18:09:55Z
dash.affiliation.other	HMS^Psychiatry-McLean Hospital	en_US
dash.affiliation.other	HMS^Psychiatry-McLean Hospital	en_US
dash.affiliation.other	HMS^Neurology-Massachusetts General Hospital	en_US