TY - JOUR
T1 - Reduced GABA content in the motor thalamus during effective deep brain stimulation of the subthalamic nucleus
AU - Stefani, Alessandro
AU - Fedele, Ernesto
AU - Pierantozzi, Mariangela
AU - Galati, Salvatore
AU - Marzetti, Francesco
AU - Peppe, Antonella
AU - Pastore, Francesco Saverio
AU - Bernardi, Giorgio
AU - Stanzione, Paolo
PY - 2011/4/5
Y1 - 2011/4/5
N2 - 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.
AB - 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.
KW - Antero-ventral thalamus
KW - cGMP
KW - GABA
KW - Globus pallidus
KW - Glutamate
KW - Stereotactic neurosurgery
KW - Subthalamus
KW - UPDRS
UR - http://www.scopus.com/inward/record.url?scp=82655175812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82655175812&partnerID=8YFLogxK
U2 - 10.3389/fnsys.2011.00017
DO - 10.3389/fnsys.2011.00017
M3 - Article
C2 - 21519387
AN - SCOPUS:82655175812
JO - Frontiers in Systems Neuroscience
JF - Frontiers in Systems Neuroscience
SN - 1662-5137
IS - APRIL 2011
M1 - 17
ER -