Relevant conflicts of interest/financial disclosures: Stephen J. Kish receives research funding from US NIH NIDA #25096 and a salary from the Centre for Addiction and Mental Health; Oleh Hornykiewicz received lecture travel support and honorarium from UCB Pharma S.A. Spain.
Article first published online: 4 OCT 2012
Copyright © 2012 Movement Disorder Society
Volume 27, Issue 13, pages 1618–1624, November 2012
How to Cite
Pifl, C., Kish, S. J. and Hornykiewicz, O. (2012), Thalamic noradrenaline in Parkinson's disease: Deficits suggest role in motor and non-motor symptoms. Mov. Disord., 27: 1618–1624. doi: 10.1002/mds.25109
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 27 NOV 2012
- Article first published online: 4 OCT 2012
- Manuscript Accepted: 11 JUN 2012
- Manuscript Revised: 4 JUN 2012
- Manuscript Received: 6 APR 2012
- U.S. NIH NIDA. Grant Number: DA29056
- Parkinson's disease;
- thalamic nuclei
The thalamus occupies a pivotal position within the corticobasal ganglia-cortical circuits. In Parkinson's disease (PD), the thalamus exhibits pathological neuronal discharge patterns, foremost increased bursting and oscillatory activity, which are thought to perturb the faithful transfer of basal ganglia impulse flow to the cortex. Analogous abnormal thalamic discharge patterns develop in animals with experimentally reduced thalamic noradrenaline; conversely, added to thalamic neuronal preparations, noradrenaline exhibits marked antioscillatory and antibursting activity. Our study is based on this experimentally established link between noradrenaline and the quality of thalamic neuronal discharges. We analyzed 14 thalamic nuclei from all functionally relevant territories of 9 patients with PD and 8 controls, and measured noradrenaline with high-performance liquid chromatography with electrochemical detection. In PD, noradrenaline was profoundly reduced in all nuclei of the motor (pallidonigral and cerebellar) thalamus (ventroanterior: −86%, P = .0011; ventrolateral oral: −87%, P = .0010; ventrolateral caudal: −89%, P = .0014): Also, marked noradrenaline losses, ranging from 68% to 91% of controls, were found in other thalamic territories, including associative, limbic and intralaminar regions; the primary sensory regions were only mildly affected. The marked noradrenergic deafferentiation of the thalamus discloses a strategically located noradrenergic component in the overall pathophysiology of PD, suggesting a role in the complex mechanisms involved with the genesis of the motor and non-motor symptoms. Our study thus significantly contributes to the knowledge of the extrastriatal nondopaminergic mechanisms of PD with direct relevance to treatment of this disorder. © 2012 Movement Disorder Society