caa a22 4500 60620315X CHVBK 20210128100956.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00429-014-0812-y doi (NATIONALLICENCE)springer-10.1007/s00429-014-0812-y Decrease of mGluR5 receptor density goes parallel with changes in enkephalin and substance P immunoreactivity in Huntington's disease: a preliminary investigation in the postmortem human brain [Elektronische Daten] [Balázs Gulyás, Judit Sovago, Baltazar Gomez-Mancilla, Zhisheng Jia, Csaba Szigeti, Károly Gulya, Martin Schumacher, Ralph Maguire, Fabrizio Gasparini, Christer Halldin] Group 1 metabotropic glutamate subtype 5 receptors (mGluR5) contribute to the control of motor behavior by regulating the balance between excitation and inhibition of outputs in the basal ganglia. The density of these receptors is increased in patients with Parkinson's disease and motor complications. We hypothesized that similar changes may occur in Huntington's disease (HD) and aimed at testing this hypothesis in a preliminary experimental series in postmortem human brain material obtained from HD patients. Using autoradiography, we analyzed mGluR5 density in the putamen, caudate nucleus and cerebellum (control region) in postmortem tissue samples from three patients with HD and three controls with two mGluR5-specific radioligands ([3H]ABP688 and [11C]ABP688). The density of enkephalin (Enk)- or substance P (SP)-containing neurons was assessed using immunohistochemical and cell-counting methods. [3H]ABP688 binding in HD was reduced in the caudate (−70.4%, P<0.001), in the putamen (−33.3%, P=0.053), and in the cerebellum (−8.79%, P=0.930) vs controls. Results with [11C]ABP688 were similar; there was good correlation between [11C]ABP688 and [3H]ABP688 binding ratios. Total cell density was similar in all three brain regions in HD patients and controls. Neuronal density was 69% lower in the caudate (P=0.002) and 64% lower in the putamen (P<0.001) of HD patients vs controls. Both direct and indirect pathways were affected, with ≥90% decrease in the density of Enk- and SP-containing neurons in the caudate and putamen of HD patients vs controls (P<0.001). In contrast to earlier observations in PD, in HD, compared to controls, the mGluR5 density was significantly lower in the caudate nucleus. The decrease in neuronal density suggests that neuronal loss was largely responsible for the observed decrease in mGluR5. Springer-Verlag Berlin Heidelberg, 2014 Huntington's disease nationallicence mGluR5 nationallicence Substance P nationallicence Encephalin nationallicence Autoradiography nationallicence Immunohistochemistry nationallicence Human brain nationallicence [3H]ABP688 nationallicence [11C]ABP688 nationallicence Gulyás Balázs Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut Sovago Judit Novartis Pharma AG, Basel, Switzerland aut Gomez-Mancilla Baltazar Novartis Institutes for Biomedical Research, Basel, Switzerland aut Jia Zhisheng Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut Szigeti Csaba Department of Cell Biology and Molecular Medicine, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary aut Gulya Károly Department of Cell Biology and Molecular Medicine, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary aut Schumacher Martin Novartis Pharma AG, Basel, Switzerland aut Maguire Ralph Novartis Pharma AG, Basel, Switzerland aut Gasparini Fabrizio Novartis Institutes for Biomedical Research, Basel, Switzerland aut Halldin Christer Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3043-3051 1863-2653 220:5<3043 2015 220 429 https://doi.org/10.1007/s00429-014-0812-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0812-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gulyás Balázs Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Sovago Judit Novartis Pharma AG, Basel, Switzerland aut NATIONALLICENCE 700 1- Gomez-Mancilla Baltazar Novartis Institutes for Biomedical Research, Basel, Switzerland aut NATIONALLICENCE 700 1- Jia Zhisheng Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Szigeti Csaba Department of Cell Biology and Molecular Medicine, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary aut NATIONALLICENCE 700 1- Gulya Károly Department of Cell Biology and Molecular Medicine, Faculty of Medicine and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary aut NATIONALLICENCE 700 1- Schumacher Martin Novartis Pharma AG, Basel, Switzerland aut NATIONALLICENCE 700 1- Maguire Ralph Novartis Pharma AG, Basel, Switzerland aut NATIONALLICENCE 700 1- Gasparini Fabrizio Novartis Institutes for Biomedical Research, Basel, Switzerland aut NATIONALLICENCE 700 1- Halldin Christer Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, 171 76, Stockholm, Sweden aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3043-3051 1863-2653 220:5<3043 2015 220 429