Impact of chronic subthalamic high-frequency stimulation on metabolic basal ganglia activity: a 2-deoxyglucose uptake and cytochrome oxidase mRNA study in a macaque model of Parkinson’s disease.

Wassilios Meissner, Celine Guigoni, Laetitia Cirilli, Maurice Garret, Bernard H. Bioulac, Christian E. Gross, Erwan Bezard, Abdelhamid Benazzouz
European Journal of Neuroscience. 2007-04-05; 25(5): 1492-1500
DOI: 10.1111/j.1460-9568.2007.05406.x

PubMed
Read on PubMed



1. Eur J Neurosci. 2007 Mar;25(5):1492-500.

Impact of chronic subthalamic high-frequency stimulation on metabolic basal
ganglia activity: a 2-deoxyglucose uptake and cytochrome oxidase mRNA study in a
macaque model of Parkinson’s disease.

Meissner W(1), Guigoni C, Cirilli L, Garret M, Bioulac BH, Gross CE, Bezard E,
Benazzouz A.

Author information:
(1)CNRS UMR 5227, Université Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux
Cedex, France.

The mechanisms of action of high-frequency stimulation (HFS) of the subthalamic
nucleus (STN) remain only partially understood. Hitherto, experimental studies
have suggested that STN-HFS reduces the activity of STN neurons. However, some
recent reports have challenged this view, showing that STN-HFS might also
increase the activity of globus pallidus internalis (GPi) neurons that are under
strong excitatory drive of the STN. In addition, most results emanate from
studies applying acute STN-HFS, while parkinsonian patients receive chronic
stimulation. Thus, the present study was designed to assess the effect of chronic
(10 days) STN-HFS in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated nonhuman primate. For this purpose, 2-deoxyglucose (2-DG) uptake,
a measure of global synaptic activity, was assessed in the basal ganglia and the
motor thalamus after chronic unilateral STN-HFS. Cytochrome oxidase subunit 1
(COI) mRNA expression, a marker of efferent metabolic activity, was additionally
assessed in the globus pallidus. Chronic STN-HFS (i) reversed abnormally
decreased 2-DG uptake in the STN of parkinsonian nonhuman primates, (ii) reversed
abnormally increased 2-DG accumulation in the GPi while COI mRNA expression was
increased, suggesting global activation of GPi neurons, and (iii) reversed
abnormally increased 2-DG uptake in the ventrolateral motor thalamus nucleus. The
simultaneous decrease in 2-DG uptake and increase in COI mRNA expression are
difficult to reconcile with the current model of basal ganglia function and
suggest that the mechanisms by which STN-HFS exerts its clinical benefits are
more complex than a simple reversal of abnormal activity in the STN and its
targets.

DOI: 10.1111/j.1460-9568.2007.05406.x
PMID: 17425575 [Indexed for MEDLINE]

Know more about