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Last update 2015-03-31 15:44:46.968

Marc SAVASTA PhD in Neuroscience

Course and current status

Marc Savasta is senior Research Director at INSERM (French National Health Institute). He is a neurobiologist with extensive experience in Parkinson's disease, in particular in the basal ganglia networks. His research work concerns the pathophysiology of Parkinson's disease, deep brain stimulation and neuropsychiatric disorders. He authored 80 publications that received more than 3500 citations - h index: 35 (

Marc Savasta is director of the Laboratory "Dynamic and Pathophysiology of Basal Ganglia" at the Grenoble Institute of Neuroscience (Inserm U836). He is deputy director of the Grenoble Institute of Neuroscience, member of section 69 (Neuroscience) of the Conseil National des Universités, member of the board of the French Socety of Neuroscience and of the Insternational Basal Ganglia Society.

Scientific summary

Marc Savasta's research work has always been interested in the pathophysiology of Parkinson's disease (PD), particularly the study of the plasticity of the dopaminergic (DA) nigrostriatal system in the rat and more recently the mechanisms underlying the effectiveness of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) for the correction of motor symptoms of the disease.

The research he conducted from 1984 to 1999 on the plasticity of the DA system allowed me to characterize a large number of post-lesional changes following DA denervation and to show that these alterations could be corrected by the implantation in the deafferented striatum of embryonic DA neurons. After having explored the mechanisms of plasticity induced by these neuronal grafting, he developed an animal model to reproduce the pre-symptomatic PD situation involving many compensatory mechanisms. He was able to show that spared DA neurons: 1) were able to modulate the responsiveness of deafferented striatal areas in order to compensate, at a functional level, the deficit induced by the degenerative process, and 2) had a spontaneous sprouting in the deafferented striatum, for post-lesional time long enough (6 months), suggesting the ability of adult DA neurons to return to growth. He also have studied during this period the possibility of compensation/repair/ functional neuroprotection of the injured DA nigrostriatal pathway, through neurotrophic factors, particularly in order to facilitate the sprouting of collaterals from spared DA neurons. He was able to show that the administration of GDNF (via a lentivirus) improved locomotor impairments induced by the DA denervation in rats, confirming the importance of this approach for therapeutic issues.

Since 1999 until today, his research focuses on mechanisms of deep brain stimulation (DBS) in PD. This DBS represents a typical example of what is called functional therapy and has emerged as a new therapeutic concept for neuromodulation of the central nervous system (CNS). Indeed, if a clinical sign is associated with a focal brain dysfunction, it can be modified by stimulating the brain area involved. It appears today that DBS is applied to certain movement, behavior and mood disorders. It has the advantage to be both a pathophysiological and therapeutic tool. STN-DBS, in the case of the PD, revealed the involvement of major circuits of the basal ganglia (BG) in the modulation of abnormal movements. Understanding its mechanisms of action and its effectiveness represent a major challenge, not only for the clinical treatment of the disease but also for the understanding of the functionning of BG circuits and of the Central Nervous System in general. During this period, he was one of the pioneers to demonstrate, through an experimental work combining innovative integrated approaches in Neuroscience (in vivo neurochemistry, electrophysiology, neuroanatomy quantitative cellular and molecular pharmacology ...) and the use of animal models of PD in rats that STN HFS, could not be related to a direct inhibition of neurons in the STN, but rather to the inhibition of output structures of BG involving GABA. The major effect of GABA can be explained by the stimulation of GABA fibers of passage, the pallido-nigral ones, in the vicinity of the STN and/or anatomo-functional organization of synaptic contacts involving the functional balance between GABA and glutamate in the substantia nigra, a major output structure of subcortical motor circuits. These results were subsequently confirmed by numerous other national and international research teams. However, the mechanisms of this DBS are still far from being elucidated and raise many pathophysiological questions about interactions between neuronal and glial networks involved in the functioning of the three main functional loops, cognitive, limbic and motor of the basal ganglia. Today, PD is no more considered as a disease affecting only the movement. Indeed, the behavioral disorders such as apathy, depression and anxiety are today considered PD as a neuropsychiatric disease. In addition, these neuropsychiatric disorders can be revealed or exacerbated by conventional drug treatment (L-Dopa, dopamine agonists) or the DBS. 

Since 2009 and through clinical investigations, neuropsychological and fundamental approaches his translational research tries to understand the pathophysiological mechanisms that underly these disorders in PD patients, ranging from hypo-(apathy) to hyper-dopaminergic (characterized by compulsive and addictive behaviour such as the dopamine dysregulation syndrome (DDS)). These disorders are a major public health issue, because they are at the origin of the deterioration of the quality of life of patients. In close interaction with clinicians, his research group developed over the past four years a rodent model of these disorders, injuring selectively and partially the DA neurons of the mesocorticolimbic system. In addition, the induction of DDS by dopaminergic treatments on the basis of such an animal model opens interesting perspectives, not only to better understand the pathophysiology of psychiatric disorders in Parkinson's disease but also for research strategies relevant related to addiction.

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