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Séminaire impromptu - Angela CenciRole of striatal pathways in the response to Parkinson´s disease therapy

Abstract :


 Parkinson’s disease (PD) patients experience loss of normal motor function (hypokinesia),
but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming the indirect or the direct pathway, respectively. This lecture will present a study testing the above hypothesis in mouse models of PD and L-DOPA-induced dyskinesia by means of pathway-specific chemogenetic stimulation. Briefly, the results of this study indicate that therapeutic and dyskinetic responses to L-DOPA are modulated by both pathways, which have opposing but complementary roles. These results have important implications for the design of antiparkinsonian and antidyskinetic treatments. 

Selected publications

Last publications...
Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson's disease therapy.Alcacer C, Andreoli L, Sebastianutto I, Jakobsson J, Fieblinger T, Cenci MA.J Clin Invest. 2017 Feb 1;127(2):720-734. doi: 10.1172/JCI90132.

 Validation of an improved scale for rating l-DOPA-induced dyskinesia in the mouse and effects of specific dopamine receptor antagonists.Sebastianutto I, Maslava N, Hopkins CR, Cenci MA.Neurobiol Dis. 2016 Dec;96:156-170. doi: 10.1016/j.nbd.2016.09.001.

 Dissociation of metabolic and hemodynamic levodopa responses in the 6-hydroxydopamine rat model.Lerner RP, Bimpisidis Z, Agorastos S, Scherrer S, Dewey SL, Cenci MA, Eidelberg D.Neurobiol Dis. 2016 Dec;96:31-37. doi: 10.1016/j.nbd.2016.08.010.

 Dramatic differences in susceptibility to l-DOPA-induced dyskinesia between mice that are aged before or after a nigrostriatal dopamine lesion.Bez F, Francardo V, Cenci MA.Neurobiol Dis. 2016 Oct;94:213-25. doi: 10.1016/j.nbd.2016.06.005.

 M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia.Shen W, Plotkin JL, Francardo V, Ko WK, Xie Z, Li Q, Fieblinger T, Wess J, Neubig RR, Lindsley CW, Conn PJ, Greengard P, Bezard E, Cenci MA, Surmeier DJ.Neuron. 2016 Jun 1;90(5):1139. doi: 10.1016/j.neuron.2016.05.017. No abstract available.

Scientific focus :

Current position and affiliation:
Professor of Experimental Medical Research, Lund University (LU)
Research Group Leader, Basal Ganglia Pathophysiology Unit, LU
http://www.med.lu.se/expmed/forskning/basala_gangliernas_patofysiologi,
100% appointment for research

Lund University,  (Sweden)