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 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.
Document type :
Journal articles
Liste complète des métadonnées
Contributor : Chantal Guerin <>
Submitted on : Tuesday, June 13, 2017 - 10:54:38 AM
Last modification on : Thursday, January 11, 2018 - 6:25:42 AM

Links full text




Matthieu F Bastide, Christelle Glangetas, Evelyne Doudnikoff, Qin Li, Mathieu Bourdenx, et al.. Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia.. Scientific Reports, Nature Publishing Group, 2017, 7 (1), pp.2348. ⟨10.1038/s41598-017-02572-9⟩. ⟨hal-01537926⟩



Record views