title: Dopamine and noradrenaline, but not serotonin, in the human claustrum are greatly reduced in patients with Parkinson's disease: possible functional implications.
abstract: In the human brain, the claustrum is a small subcortical telencephalic nucleus, situated between the insular cortex and the putamen. A plethora of neuroanatomical studies have shown the existence of dense, widespread, bidirectional and bilateral monosynaptic interconnections between the claustrum and most cortical areas. A rapidly growing body of experimental evidence points to the integrative role of claustrum in complex brain functions, from motor to cognitive. Here, we examined for the first time, the behaviour of the classical monoamine neurotransmitters dopamine, noradrenaline and serotonin in the claustrum of the normal autopsied human brain and of patients who died with idiopathic Parkinson's disease (PD). We found in the normal claustrum substantial amounts of all three monoamine neurotransmitters, substantiating the existence of the respective brain stem afferents to the claustrum. In PD, the levels of dopamine and noradrenaline were greatly reduced by 93 and 81%, respectively. Serotonin levels remained unchanged. We propose that by virtue of their projections to the claustrum, the brain stem dopamine, noradrenaline and serotonin systems interact directly with the cortico-claustro-cortical information processing mechanisms, by-passing their (parallel) routes via the basal ganglia-thalamo-cortical circuits. We suggest that loss of dopamine and noradrenaline in the PD claustrum is critical in the aetiology of both the motor and the non-motor symptoms of PD.
authors.affiliation: Centre for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Waehringerstrasse 13A, A-1090, Vienna, Austria.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Sitte
authors.affiliation: Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Pifl
authors.affiliation: Division of Neurology, Saskatchewan Movement Disorders Program, Saskatoon Health Region, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rajput
authors.affiliation: Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Heide
authors.initials: H
authors.lastname: Hörtnagl
authors.affiliation: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Junchao
authors.initials: J
authors.lastname: Tong
authors.affiliation: GKOL Inc., Poway, CA, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Lloyd
authors.affiliation: Human Brain Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: Centre for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Oleh
authors.initials: O
authors.lastname: Hornykiewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism
chemical_list: D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine
keywords: claustral circuitry; human brain disorders; monoamine neurotransmitters; neurochemistry; post-mortem