Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation

Acta Neuropathologica
Natalie MatosinKelly A Newell

Abstract

Knockout of genes encoding metabotropic glutamate receptor 5 (mGluR5) or its endogenous regulators, such as Norbin, induce a schizophrenia-like phenotype in rodents, suggesting dysregulation of mGluR5 in schizophrenia. Human genetic and pharmacological animal studies support this hypothesis, but no studies have explored mGluR5 dysfunction at the molecular level in the postmortem schizophrenia brain. We assessed mGluR5 mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC) using a large cohort of schizophrenia and control subjects (n = 37/group), and additionally measured protein levels of recently discovered mGluR5 endogenous regulators, Norbin (neurochondrin), Tamalin (GRASP-1), and Preso1 (FRMPD4), which regulate mGluR5 localization, internalization and signaling. While mGluR5 mRNA expression was unchanged, mGluR5 protein levels were significantly higher in schizophrenia subjects compared to controls (total: +22%; dimer: +54%; p < 0.001). Conversely, mGluR5 regulatory proteins were expressed at lower levels in schizophrenia subjects compared to controls (Norbin -37%, p < 0.001; Tamalin -30%, p = 0.084; Preso1 -29%, p = 0.001). mGluR5 protein was significantly associated with mGluR5 mRNA and mGluR5 endogenous re...Continue Reading

References

Nov 8, 1996·The Journal of Biological Chemistry·C RomanoK L O'Malley
Oct 19, 1999·Biochimica Et Biophysica Acta·R MochizukiK Murakami
Sep 4, 2003·Genome Biology·Dov GreenbaumMark Gerstein
Jun 24, 2004·Molecular Pharmacology·Graeme Milligan
May 29, 2007·Biological Psychiatry·Corrado CortiFrancesco Ferraguti
Sep 6, 2007·Journal of Neuroscience Research·Mei HanXu-Feng Huang
Nov 23, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Monica Beneyto, James H Meador-Woodruff
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hyun Woo LeeEunjoon Kim
Jan 16, 2010·The Australian and New Zealand Journal of Psychiatry·Cynthia Shannon WeickertClive Harper
Jul 6, 2010·Journal of Psychiatric Research·Ilja SpellmannMichael Riedel
Jul 27, 2010·Schizophrenia Research·Rajiv TandonMatcheri S Keshavan
Feb 19, 2011·Communicative & Integrative Biology·Hong WangMarc Flajolet
Oct 11, 2011·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Katrina Weston-GreenChao Deng
May 9, 2012·Nature Neuroscience·Jia-Hua HuPaul F Worley
May 26, 2012·Nature Neuroscience·Jelena Radulovic, Natalie C Tronson
Sep 19, 2012·Schizophrenia Bulletin·Daniel C Javitt
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Driss El MoustaineJean-Philippe Pin
Oct 17, 2012·Molecular Psychiatry·C S WeickertT W Weickert
Dec 21, 2012·Neuroscience and Biobehavioral Reviews·Natalie Matosin, Kelly A Newell
May 31, 2013·Frontiers in Cellular Neuroscience·Vibeke S CattsCynthia Shannon Weickert
Oct 5, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Robert E McCullumsmithJames H Meador-Woodruff

❮ Previous
Next ❯

Citations

Jul 20, 2016·NPJ Schizophrenia·Natalie MatosinKelly A Newell
Nov 1, 2016·Molecular Neurobiology·Lucia CaffinoFabio Fumagalli
Jun 14, 2019·Schizophrenia Bulletin·Amber Berdenis van BerlekomLot D de Witte
Sep 2, 2016·European Archives of Psychiatry and Clinical Neuroscience·Alessia LuoniDragos Inta
Sep 18, 2020·Expert Opinion on Emerging Drugs·Marco PozziMaria Nobile
Oct 27, 2017·Scientific Reports·Yali XuXuefeng Wang
Sep 15, 2018·Molecular Psychiatry·Hoau-Yan WangChang-Gyu Hahn
Dec 16, 2018·Cellular and Molecular Neurobiology·Lauren KostenSteven Staelens
Jan 27, 2019·Molecular Psychiatry·Madeline R Scott, James H Meador-Woodruff
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Carolina GubertAnthony J Hannan
Nov 26, 2020·International Journal of Molecular Sciences·Paulina Cieślik, Joanna M Wierońska

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here