Summary
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.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12: 366–375
Basser PJ, Roth BJ (2000) New currents in electrical stimulation of excitable tissues. Annu Rev Biomed Eng 2: 377–397
Brown P, Mazzone P, Oliviero A, Altibrandi MG, Pilato F, Tonali PA, Di Lazzaro V (2004) Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson’s disease. Exp Neurol 188: 480–490
Bruet N, Windels F, Carcenac C, Feuerstein C, Bertrand A, Poupard A, et al. (2003) Neurochemical mechanisms induced by high frequency stimulation of the subthalamic nucleus: increase of extracellular striatal glutamate and GABA in normal and hemiparkinsonian rats. J Neuropathol Exp Neurol 62: 1228–1240
Fahn S, Elton RL, and Members of the UPDRS development committee (1987) The Unified Parkinson’s disease rating scale. In: Fahn S, Mardsen CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease. Mac Millan Healthcare Information, Florham Park, NY, pp 153–163
Fedele E, Raiteri M (1999) In vivo studies of the cerebral glutamate receptor=NO=cGMP pathway. Prog Neurobiol 58: 89–120
Fedele E, Mazzone P, Stefani A, Bassi A, Ansaldo MA, Reiteri M, et al. (2001) Microdialysis in Parkinsonian patient basal ganglia: acute apomorphineinduced clinical and electrophysiological effects not paralleled by changes in the release of neuroactive amino acids. Exp Neurol 167: 356–365
Filali M, Hutchison WD, Palter VN, Lozano AM, Dostrovsky JO (2004) Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus. Exp Brain Res 156: 274–281
Gill SS, Heywood P (1997) Bilateral dorsolateral subthalamotomy for advanced Parkinson’s disease. Lancet 350: 1224
Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL (2003) Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci 23: 1916–1923
Hershey T, Revilla FJ, Wernle AR, McGee-Minnich L, Antenor JV, Videen TO, et al. (2003) Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology 61: 816–821
Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, et al. (2004) Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidences from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 24: 7–16
Jonkers N, Sarre S, Ebinger G, Michotte Y (2002) MK801 suppresses the L-DOPA-induced increase of glutamate in striatum of hemi-parkinsonian rata. Brain Res 926: 149–155
Kita H, Chang HT, Kitai ST (1983) The morphology of intracellularly labeled rat subthalamic neurons: a light microscopic analysis. J Comp Neurol 215: 245–257
Levy R, Lang AE, Dostrovsky JO, Pahapill P, Romas J, Saint-Cyr J, et al. (2001) Lidocaine and muscimole microinjections in STN reverse parkinsonian symptoms. Brain 124: 2105–2118
Limousin P, Gree J, Pollak P, Rothwell J, Benabid AL, Frackowiak R (1997) Changes in cerebral activity pattern due to STN or GPi stimulation in Parkinson’s disease. Ann Neurol 42: 283–291
MacKinnon CD, Webb RM, Silberstein P, Tisch S, Asselman P, Rothwell JC (2005) Stimulation through electrodes implanted near the subthalamic nucleus activates projections to motor areas of cerebral cortex in patients with Parkinson’s disease. Eur J Neurosci 21: 1394–1402
Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA, et al. (1989) Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine. Neuroscience 32: 213–226
Pepicelli O, Brescia A, Gherzi E, Raiteri M, Fedele E (2004) GABA(A), but not NMDA, receptors modulate in vivo NO-mediated cGMP synthesis in the rat cerebral cortex. Neuropharmacology 46: 480–489
Peppe A, Pierantozzi M, Bassi A, Altibrandi MG, Brusa L, Stefani A, et al. (2004) Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease. J Neurosurg 101: 195–200
Pierantozzi M, Mazzone P, Bassi A, Rossini PM, Peppe A, Altibrandi MG, et al. (1999) The effect of deep brain stimulation on the frontal N30 component of somatosensory evoked potentials in advanced Parkinson’s disease patients. Clin Neurophysiol 110: 1700–1707
Pierantozzi M, Palmieri MG, Mazzone P, Marciani MG, Rossini PM, Stefani A, et al. (2002) Deep brain stimulation of both subthalamic nucleus and internal globus pallidus restores intracortical inhibition in Parkinson’s disease paralleling apomorphine effects: a paired magnetic stimulation study. Clin Neurophysiol 113: 108–113
Plonsey R, Barr RC (eds) (2000) Bioelectricity, a quantitative approach. Plenum Press, New York
Rattay F (1999) The basic mechanism for the electrical stimulation of the nervous system. Neuroscience 89: 335–346
Sidibé M, Bevan MD, Bolam JP, Smith Y (1997) Efferent connection of the internal globus pallidus in the squirrel monkey. I. Topography and synaptic organization of the pallidothalamic projection. J Comp Neurol 382: 323–347
Stefani A, Fedele E, Galati S, Pepicelli O, Frasca S, Pierantozzi M, et al. (2005) Subthalamic stimulation activates internal pallidus: evidence from cGMP microdialysis in PD patients. Ann Neurol 57: 448–452
Welter ML, Houeto JL, Bonnet AM, Bejjani PB, Mesnage V, Dormont D, et al. (2004) Effects of high-frequency stimulation on subthalamic neuronal activity in parkinsonian patients. Arch Neurol 61: 89–96
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag
About this paper
Cite this paper
Stefani, A. et al. (2006). Deep brain stimulation in Parkinson’s disease patients: biochemical evidence. In: Riederer, P., Reichmann, H., Youdim, M.B.H., Gerlach, M. (eds) Parkinson’s Disease and Related Disorders. Journal of Neural Transmission. Supplementa, vol 70. Springer, Vienna . https://doi.org/10.1007/978-3-211-45295-0_60
Download citation
DOI: https://doi.org/10.1007/978-3-211-45295-0_60
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-28927-3
Online ISBN: 978-3-211-45295-0
eBook Packages: MedicineMedicine (R0)