title: Changes in the expression of neurotransmitter receptors in Parkin and DJ-1 knockout mice--A quantitative multireceptor study.
abstract: Parkinson's disease (PD) is a well-characterized neurological disorder with regard to its neuropathological and symptomatic appearance. At the genetic level, mutations of particular genes, e.g. Parkin and DJ-1, were found in human hereditary PD with early onset. Neurotransmitter receptors constitute decisive elements in neural signal transduction. Furthermore, since they are often altered in neurological and psychiatric diseases, receptors have been successful targets for pharmacological agents. However, the consequences of PD-associated gene mutations on the expression of transmitter receptors are largely unknown. Therefore, we studied the expression of 16 different receptor binding sites of the neurotransmitters glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine by means of quantitative receptor autoradiography in Parkin and DJ-1 knockout mice. These knockout mice exhibit electrophysiological and behavioral deficits, but do not show the typical dopaminergic cell loss. We demonstrated differential changes of binding site densities in eleven brain regions. Most prominently, we found an up-regulation of GABA(B) and kainate receptor densities in numerous cortical areas of Parkin and DJ-1 knockout mice, as well as increased NMDA but decreased AMPA receptor densities in different brain regions of the Parkin knockout mice. The alterations of three different glutamate receptor types may indicate the potential relevance of the glutamatergic system in the pathogenesis of PD. Furthermore, the cholinergic M1, M2 and nicotinic receptors as well as the adrenergic α2 and the adenosine A(2A) receptors showed differentially increased densities in Parkin and DJ-1 knockout mice. Taken together, knockout of the PD-associated genes Parkin or DJ-1 results in differential changes of neurotransmitter receptor densities, highlighting a possible role of altered non-dopaminergic, and in particular of glutamatergic neurotransmission in PD pathogenesis.
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, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Amunts
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schleicher
authors.affiliation: Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Palomero-Gallagher
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: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology; D054464:Peroxiredoxins / Q000172:deficiency / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics*
chemical_list: D015513:Oncogene Proteins; D017981:Receptors, Neurotransmitter; D054464:Peroxiredoxins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: DJ-1; Parkin; Parkinson’s disease; knockout mouse; neurotransmitter receptor