Scientific Reports (May 2017)

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

DOI
https://doi.org/10.1038/s41598-017-02572-9
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 7

Abstract

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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.