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Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus.
MedLine Citation:
PMID:  21519387     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (-30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy.
Authors:
Alessandro Stefani; Ernesto Fedele; Mariangela Pierantozzi; Salvatore Galati; Francesco Marzetti; Antonella Peppe; Francesco Saverio Pastore; Giorgio Bernardi; Paolo Stanzione
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Publication Detail:
Type:  Journal Article     Date:  2011-04-05
Journal Detail:
Title:  Frontiers in systems neuroscience     Volume:  5     ISSN:  1662-5137     ISO Abbreviation:  Front Syst Neurosci     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-26     Completed Date:  2011-07-14     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  101477946     Medline TA:  Front Syst Neurosci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  17     Citation Subset:  -    
Affiliation:
Istituto di Ricovero e Cura a Carattere Scientifico Fondazione S. Lucia, Roma, Italy.
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