RESTORATIVE PLASTICITY AT CORTICOSTRIATAL EXCITATORY SYNAPSES A project funded by the European Union Seventh Framework Programme FP7/2007-2013 under grant.

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Presentation transcript:

RESTORATIVE PLASTICITY AT CORTICOSTRIATAL EXCITATORY SYNAPSES A project funded by the European Union Seventh Framework Programme FP7/ under grant agreement n° Graph and Illustrations: The Visual Agency

PARKINSON’S DISEASE (PD) is one of the most common chronic progressive neurodegenerative diseases has a prevalence of 1.2 million people in Europe and an annual cost of 11 billion Euros, being one of the 12 most costly brain diseases in Europe Di Luca M, Baker M, Corradetti R, Kettenmann H, Mendlewicz J, Olesen J, Ragan I, Westphal M. Eur J Neurosci. 2011

COST OF DISORDERS OF THE BRAIN IN EUROPE Estimates in 2004 Estimates in 2010 European Neuropsychopharmacology (2011) 21, (1) Referred to as “effective disorders” in 2005, (2) includes only incident cases in 2010, (3) weighted mean from all countries and diagnoses (5) including also persons with zero costs, (6) excluding indirect costs, (7) excluding PTSD.

COST OF DISORDERS OF THE BRAIN IN EUROPE Estimates in 2004 Estimates in 2010 European Neuropsychopharmacology (2011) 21, (1) Referred to as “effective disorders” in 2005, (2) includes only incident cases in 2010, (3) weighted mean from all countries and diagnoses (5) including also persons with zero costs, (6) excluding indirect costs, (7) excluding PTSD. The cost of brain diseases in Europe has been estimated 798 billion euros (The economic cost of brain disorders in Europe. Olesen et al, Eur J Neurol. 2012)

WHAT DO WE ASK TO RESEARCH? How to impact on disease onset and progression, to effectively help those citizens LEAVING WITH PD A strong translational character: Understanding the brain functioning at molecular, cellular and system level is essential to unravel pathogenesis of brain disease

A spine is moving! A confocal microscopy analysis

IN VITRO... Pure Striatum co-cultured with cortex

IN VIVO... AAV α-synuclein model of PD: progressive neurodegeneration

3 NOVEL HYPOTHESES TO CURE

METABOTROPIC GLUTAMATE RECEPTOR TYPE 5 (mGluR5) AS A TARGET FOR THE TREATMENT OF L-DOPA-INDUCED DYSKINESIA

SYNAPTIC LOCALIZATOR OF NR2A SUBUNIT IN CHRONIC L-DOPA TREATED ANIMALS MODULATES DYSKINETIC MOTOR BEHAVIOUR TAT-2A TAT-2A(-SDV) Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg - Lys-Met-Pro-Ser-Ile-Glu-Ser-Asp-Val Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg - Lys-Met-Pro-Ser-Ile-Glu TATNR2A C-tail

REBALANCE OF STRIATAL NMDA/AMPA RECEPTOR RATIO UNDERLIES THE REDUCED EMERGENCE OF DYSKINESIA DURING D2-LIKE DOPAMINE AGONIST TREATMENT

THE REPLACES CONSORTIUM Monica Di LucaUniversity of Milano - ItalyPaolo CalabresiFondazione Santa Lucia - ItalyEckart GundelfingerLeibniz Institute for Neurobiology - GermayEtienne HirschINSERM - FranceStephen DunnettCardiff University - United KingdomAnders BjorklundLund University - LU SwedenJose ObesoUniversity of Navarra - SpainJohn RothwellUniversity College London - UCL United KingdomLaurent Fagni Centre National de la Recherche Scientifique - FranceMary BakerEuropean Parkinson's Disease Association Carla FinocchiaroCF consulting Srl - Italy THANK YOU Graph and Illustrations: The Visual Agency