title: Thalamic noradrenaline in Parkinson's disease: deficits suggest role in motor and non-motor symptoms.
abstract: 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.
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Pifl
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.forename: Oleh
authors.initials: O
authors.lastname: Hornykiewicz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016923:Cell Death; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000473:pathology; D009638:Norepinephrine / Q000172:deficiency*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology
chemical_list: D009638:Norepinephrine