title: 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study.
abstract: The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [(3)H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression.
authors: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen University Hospital, 2300 Copenhagen, Denmark.
authors: Nadja Bredo
authors: NB
authors: Rasmussen
authors: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen University Hospital, 2300 Copenhagen, Denmark.
authors: Mikkel Vestergaard
authors: MV
authors: Olesen
authors: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen University Hospital, 2300 Copenhagen, Denmark.
authors: Tomasz
authors: 0000-0001-5453-1817
authors: T
authors: Brudek
authors: Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors: Per
authors: P
authors: Plenge
authors: Department of Drug Design and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors: Anders Bue
authors: AB
authors: Klein
authors: Department of Neurodegeneration, Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
authors: Jenny E
authors: JE
authors: Westin
authors: Department of Neurodegeneration, Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
authors: Karina
authors: K
authors: Fog
authors: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen and Mental Health Center Copenhagen, 2200 Copenhagen, Denmark.
authors: Gitta
authors: 0000-0001-6981-7885
authors: G
authors: Wörtwein
authors: Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospitals, Copenhagen University Hospital, 2300 Copenhagen, Denmark.
authors: Susana
authors: 0000-0001-7940-6246
authors: S
authors: Aznar