title: Neurodevelopmental Expression Profile of Dimeric and Monomeric Group 1 mGluRs: Relevance to Schizophrenia Pathogenesis and Treatment.
abstract: Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Lum
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.|School of Psychology, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fernandez
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.|Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10 Munich Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Matosin
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Andrews
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Biological Sciences, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.
authors.forename: Lezanne
authors.initials: L
authors.lastname: Ooi
authors.affiliation: Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.|School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.|Schizophrenia Research Institute, Sydney, NSW 2010 Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Newell
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000196:embryology*; D008297:Male; D055495:Neurogenesis; D010622:Phencyclidine / Q000009:adverse effects* / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000196:embryology*; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000096:biosynthesis*; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis*; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism
chemical_list: C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D010622:Phencyclidine