Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia

Abstract A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in...

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Autores principales:	Matthieu F. Bastide, Christelle Glangetas, Evelyne Doudnikoff, Qin Li, Mathieu Bourdenx, Pierre-Olivier Fernagut, Éric C. Dumont, François Georges, Erwan Bézard
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Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/47db4083299b4a6a87751b98dad6c488
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spelling	oai:doaj.org-article:47db4083299b4a6a87751b98dad6c4882021-12-02T15:05:24ZInvolvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia10.1038/s41598-017-02572-92045-2322https://doaj.org/article/47db4083299b4a6a87751b98dad6c4882017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02572-9https://doaj.org/toc/2045-2322Abstract A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson’s disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology.Matthieu F. BastideChristelle GlangetasEvelyne DoudnikoffQin LiMathieu BourdenxPierre-Olivier FernagutÉric C. DumontFrançois GeorgesErwan BézardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthieu F. Bastide Christelle Glangetas Evelyne Doudnikoff Qin Li Mathieu Bourdenx Pierre-Olivier Fernagut Éric C. Dumont François Georges Erwan Bézard Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
description	Abstract A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson’s disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology.
format	article
author	Matthieu F. Bastide Christelle Glangetas Evelyne Doudnikoff Qin Li Mathieu Bourdenx Pierre-Olivier Fernagut Éric C. Dumont François Georges Erwan Bézard
author_facet	Matthieu F. Bastide Christelle Glangetas Evelyne Doudnikoff Qin Li Mathieu Bourdenx Pierre-Olivier Fernagut Éric C. Dumont François Georges Erwan Bézard
author_sort	Matthieu F. Bastide
title	Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
title_short	Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
title_full	Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
title_fullStr	Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
title_full_unstemmed	Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
title_sort	involvement of the bed nucleus of the stria terminalis in l-dopa induced dyskinesia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/47db4083299b4a6a87751b98dad6c488
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Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia

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