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

Matthieu F. Bastide, Christelle Glangetas, Evelyne Doudnikoff, Qin Li, Mathieu Bourdenx, Pierre-Olivier Fernagut, Éric C. Dumont, François Georges, Erwan Bézard
Sci Rep. 2017-05-24; 7(1):
DOI: 10.1038/s41598-017-02572-9

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1. Sci Rep. 2017 May 24;7(1):2348. doi: 10.1038/s41598-017-02572-9.

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

Bastide MF(1)(2), Glangetas C(1)(2), Doudnikoff E(1)(2), Li Q(3)(4), Bourdenx
M(1)(2), Fernagut PO(1)(2), Dumont ÉC(5), Georges F(1)(2), Bézard E(6)(7)(8)(9).

Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000, Bordeaux, France.
(2)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux,
France.
(3)Motac neuroscience Ltd, Manchester, UK.
(4)Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing,
China.
(5)Department of Biomedical and Molecular Sciences, Queen’s University, Kingston,
Canada.
(6)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000, Bordeaux, France. .
(7)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux,
France. .
(8)Motac neuroscience Ltd, Manchester, UK. .
(9)Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing,
China. .

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.

DOI: 10.1038/s41598-017-02572-9
PMCID: PMC5443775
PMID: 28539659


Auteurs Bordeaux Neurocampus