title: High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson's disease.
abstract: BACKGROUND
  It has been suggested that glutamatergic system hyperactivity may be related to the pathogenesis of Parkinson's disease (PD). Vesicular glutamate transporters (VGLUT1-3) import glutamate into synaptic vesicles and are key anatomical and functional markers of glutamatergic excitatory transmission. Both VGLUT1 and VGLUT2 have been identified as definitive markers of glutamatergic neurons, but VGLUT 3 is also expressed by non glutamatergic neurons. VGLUT1 and VGLUT2 are thought to be expressed in a complementary manner in the cortex and the thalamus (VL/VM), in glutamatergic neurons involved in different physiological functions. Chronic high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced PD. STN-HFS is highly effective, but its mechanisms of action remain unclear. This study examines the effect of STN-HFS on VGLUT1-3 expression in different brain nuclei involved in motor circuits, namely the basal ganglia (BG) network, in normal and 6-hydroxydopamine (6-OHDA) lesioned rats.
  
  
  RESULTS
  Here we report that: 1) Dopamine(DA)-depletion did not affect VGLUT1 and VGLUT3 expression but significantly decreased that of VGLUT2 in almost all BG structures studied; 2) STN-HFS did not change VGLUT1-3 expression in the different brain areas of normal rats while, on the contrary, it systematically induced a significant increase of their expression in DA-depleted rats and 3) STN-HFS reversed the decrease in VGLUT2 expression induced by the DA-depletion.
  
  
  CONCLUSIONS
  These results show for the first time a comparative analysis of changes of expression for the three VGLUTs induced by STN-HFS in the BG network of normal and hemiparkinsonian rats. They provide evidence for the involvement of VGLUT2 in the modulation of BG cicuits and in particular that of thalamostriatal and thalamocortical pathways suggesting their key role in its therapeutic effects for alleviating PD motor symptoms.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique et Physiopathologie des Ganglions de la Base, Grenoble F-38043, Cedex 9, France. marc.savasta@ujf-grenoble.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Favier
authors.forename: Carole
authors.initials: C
authors.lastname: Carcenac
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drui
authors.forename: Sabrina
authors.initials: S
authors.lastname: Boulet
authors.forename: Salah
authors.initials: S
authors.lastname: El Mestikawy
authors.forename: Marc
authors.initials: M
authors.lastname: Savasta
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007150:Immunohistochemistry; D008297:Male; D009434:Neural Pathways / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000378:metabolism*; D050496:Vesicular Glutamate Transport Proteins / Q000096:biosynthesis*
chemical_list: D050496:Vesicular Glutamate Transport Proteins