Metabolic and electrophysiological changes in the basal ganglia of transgenic Huntington’s disease rats
Neurobiology of Disease. 2012-12-01; 48(3): 488-494
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Vlamings R(1), Benazzouz A, Chetrit J, Janssen ML, Kozan R, Visser-Vandewalle V, Steinbusch HW, von Hörsten S, Temel Y.
(1)Department of Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Huntington’s disease (HD) is characterized by neuronal loss in the striatum,
ultimately leading to an ‘imbalance’ in the electrical activity of the basal
ganglia-thalamocortical circuits. To restore this ‘imbalance’ in HD patients,
which is held responsible for (some) of the motor symptoms, different basal
ganglia nuclei have been targeted for surgical therapies, such as ablative
surgery and deep brain stimulation. However, evidence to target brain nuclei for
surgical therapies in HD is lacking. We reasoned that a neuronal and metabolic
mapping of the basal ganglia nuclei could identify a functional substrate for
therapeutic interventions. Therefore, the aim of the present study was to
investigate the metabolic and neuronal activity of basal ganglia nuclei in a
transgenic rat model of HD (tgHD). Subjects were 10-12 month old tgHD rats and
wildtype littermates. We examined the striatum, globus pallidus, entopeduncular
nucleus, the subthalamic nucleus and substantia nigra at different levels.
First, we determined the overall neuronal activity at a supracellular level, by
cytochrome oxidase histochemistry. Secondly, we determined the subcellular
metabolic activity, by immunohistochemistry for peroxisome
proliferator-activated receptor-γ transcription co-activator (PGC-1α), a key
player in the mitochondrial machinery. Finally, we performed extracellular
single unit recordings in the nuclei to determine the cellular activity. In tgHD
rats, optical density analysis showed a significantly increased cytochrome
oxidase levels in the globus pallidus and subthalamic nucleus when compared to
controls. PGC-1α expression was only enhanced in the subthalamic nucleus and
electrophysiological recordings revealed decreased firing frequency of the
majority of the neurons in the globus pallidus and increased firing frequency of
the majority of the neurons in the subthalamic nucleus. Altogether, our results
suggest that the globus pallidus and subthalamic nucleus play a role in the
neurobiology of HD and can be potential targets for therapeutic interventions.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22813864 [Indexed for MEDLINE]