title: Neurotransmitter receptor density changes in Pitx3ak mice--a model relevant to Parkinson's disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of neurotransmitter receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative receptor autoradiography was used to characterize 19 different receptor binding sites in eleven brain regions in order to understand receptor changes on a systemic level. We demonstrated striking differential changes of neurotransmitter receptor densities for numerous receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α1 and dopaminergic D2/D3 receptors were differentially altered. These results present novel insights into the expression of neurotransmitter receptors in Pitx3(ak) mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3(ak) mice as an appropriate new model to investigate the role of neurotransmitter receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology.
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital, RWTH Aachen University, and JARA - Translational Brain Medicine, D-52062 Aachen, Germany. Electronic address: je.cremer@fz-juelich.de.
authors.forename: J N
authors.initials: JN
authors.lastname: Cremer
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Cécile & Oskar Vogt Institute of Brain Research, Heinrich-Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Amunts
authors.affiliation: Helmholtz Center Munich, Institute of Developmental Genetics (IDG), Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Graw
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Piel
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Rösch
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital, RWTH Aachen University, and JARA - Translational Brain Medicine, D-52062 Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Zilles
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020734:Parkinsonian Disorders / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors; C433629:homeobox protein PITX3; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D000109:Acetylcholine; D004298:Dopamine; D004837:Epinephrine
keywords: Parkinson’s disease; Pitx3(ak); mouse model; neurotransmitter receptor