The clinical efficacy of L-DOPA and STN-DBS share a common marker: Reduced GABA content in the motor thalamus

A. Stefani, E. Fedele, J. Vitek, M. Pierantozzi, S. Galati, S. Marzetti, A. Peppe, M. S. Bassi, G. Bernardi, P. Stanzione

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

At odd with traditional views, effective sub-thalamic nucleus (STN) deep brain stimulation (DBS), in Parkinson's disease (PD) patients, may increase the discharge rate of the substantia nigra pars reticulata and the internal globus pallidus (GPi), in combination with increased cyclic guanosine monophosphate (cGMP) levels. How these changes affect the basal ganglia (BG) output to the motor thalamus, the crucial structure conveying motor information to cortex, is critical. Here, we determined the extracellular GABA concentration in the ventral anterior nucleus (VA) during the first delivery of STN-DBS (n=10) or following levodopa (LD) (n=8). Both DBS and subdyskinetic LD reversibly reduced (-30%) VA GABA levels. A significant correlation occurred between clinical score and GABA concentration. By contrast, only STN-DBS increased GPi cGMP levels. Hence, STNON and MED-ON involve partially different action mechanisms but share a common target in the VA. These findings suggest that the standard BG circuitry, in PD, needs revision as relief from akinesia may take place, during DBS, even in absence of reduced GPi excitability. However, clinical amelioration requires fast change of thalamic GABA, confirming, in line with the old model, that VA is the core player in determining thalamo-cortical transmission.

Original languageEnglish (US)
Article numbere154
JournalCell Death and Disease
Volume2
Issue number5
DOIs
StatePublished - May 2011

Bibliographical note

Funding Information:
This work has been supported by Ministero della Salute

Keywords

  • Challenge test
  • Pallido-thalamic pathway
  • Parkinson's disease
  • STN-DBS

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