title: Deep brain stimulation in Parkinson's disease patients: biochemical evidence.
abstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients augments STN-driven excitation of the internal globus pallidus (GPi). However, other DBS-induced changes are largely unknown. Here we report the biochemical effects of STN-DBS in two basal ganglia stations (putamen--PUT--and GPi) and in a thalamic relay nucleus, the anteroventral thalamus (VA). In six advanced PD patients undergoing surgery, microdialysis samples were collected from GPi, PUT and VA before, during and after one hour of STN-DBS. cGMP was measured in the GPi and PUT as an index of glutamatergic transmission, whereas GABA was measured in the VA. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in the VA (-25%). Simultaneously, cGMP extracellular concentrations were enhanced in the PUT (+200%) and GPi (+481%). DBS differentially affects fibers crossing the STN area: it activates the STN-GPi pathway while inhibiting the GPi-VA one. These findings support a thalamic dis-inhibition, as the main responsible for the clinical effect of STN-DBS. This, in turn, re-establishes a more physiological level of PUT activity.
authors.affiliation: I.R.C.C.S. Fondazione S. Lucia, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Stefani
authors.forename: E
authors.initials: E
authors.lastname: Fedele
authors.forename: S
authors.initials: S
authors.lastname: Galati
authors.forename: M
authors.initials: M
authors.lastname: Raiteri
authors.forename: O
authors.initials: O
authors.lastname: Pepicelli
authors.forename: L
authors.initials: L
authors.lastname: Brusa
authors.forename: M
authors.initials: M
authors.lastname: Pierantozzi
authors.forename: A
authors.initials: A
authors.lastname: Peppe
authors.forename: A
authors.initials: A
authors.lastname: Pisani
authors.forename: G
authors.initials: G
authors.lastname: Gattoni
authors.forename: A H
authors.initials: AH
authors.lastname: Hainsworth
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: P
authors.initials: P
authors.lastname: Stanzione
authors.forename: P
authors.initials: P
authors.lastname: Mazzone
mesh_terms: D000368:Aged; D015415:Biomarkers; D006152:Cyclic GMP / Q000378:metabolism; D046690:Deep Brain Stimulation; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000628:therapy*; D013788:Thalamus / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005680:gamma-Aminobutyric Acid; D006152:Cyclic GMP