PMID- 30176067 OWN - NLM STAT- MEDLINE DCOM- 20200422 LR - 20200422 IS - 1098-2396 (Electronic) IS - 0887-4476 (Linking) VI - 73 IP - 1 DP - 2019 Jan TI - Quantitative proteomics of forebrain subcellular fractions in fragile X mental retardation 1 knockout mice following acute treatment with 2-Methyl-6-(phenylethynyl)pyridine: Relevance to developmental study of schizophrenia. PG - e22069 LID - 10.1002/syn.22069 [doi] AB - The fragile X mental retardation 1 knockout (Fmr1 KO) mouse replicates behavioral deficits associated with autism, fragile X syndrome, and schizophrenia. Less is known whether protein expression changes are consistent with findings in subjects with schizophrenia. In the current study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics to determine the protein expression of four subcellular fractions in the forebrains of Fmr1 KO mice vs. C57BL/6 J mice and the effect of a negative allosteric modulator of mGluR5-2-Methyl-6-(phenylethynyl)pyridine (MPEP)-on protein expression. Strain- and treatment-specific differential expression of proteins was observed, many of which have previously been observed in the brains of subjects with schizophrenia. Western blotting verified the direction and magnitude of change for several proteins in different subcellular fractions as follows: neurofilament light protein (NEFL) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) in the total homogenate; heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) and heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) in the nuclear fraction; excitatory amino acid transporter 2 (EAAT2) and ras-related protein rab 3a (RAB3A) in the synaptic fraction; and ras-related protein rab 35 (RAB35) and neuromodulin (GAP43) in the rough endoplasmic reticulum fraction. Individuals with FXS do not display symptoms of schizophrenia. However, the biomarkers that have been identified suggest that the Fmr1 KO model could potentially be useful in the study of schizophrenia. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Folsom, Timothy D AU - Folsom TD AD - Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota. FAU - Higgins, LeeAnn AU - Higgins L AD - Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota. FAU - Markowski, Todd W AU - Markowski TW AD - Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota. FAU - Griffin, Timothy J AU - Griffin TJ AD - Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota. FAU - Fatemi, S Hossein AU - Fatemi SH AUID- ORCID: 0000-0002-6859-2626 AD - Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Minneapolis, Minnesota. AD - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20181003 PL - United States TA - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Fmr1 protein, mouse) RN - 0 (GAP-43 Protein) RN - 0 (Neurofilament Proteins) RN - 0 (Proteome) RN - 0 (Pyridines) RN - 0 (Ribonucleoproteins) RN - 0 (Slc1a2 protein, mouse) RN - 0 (neurofilament protein L) RN - 139135-51-6 (Fragile X Mental Retardation Protein) RN - 7VC0YVI27Y (6-methyl-2-(phenylethynyl)pyridine) RN - EC 3.1.4.37 (2',3'-Cyclic Nucleotide 3'-Phosphodiesterase) RN - EC 3.1.4.37 (Cnp protein, mouse) RN - EC 3.6.5.2 (rab GTP-Binding Proteins) SB - IM MH - 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase/genetics/metabolism MH - Animals MH - Excitatory Amino Acid Antagonists/*pharmacology MH - Excitatory Amino Acid Transporter 2/genetics/metabolism MH - Fragile X Mental Retardation Protein/*genetics MH - GAP-43 Protein/genetics/metabolism MH - Gene Deletion MH - Mice MH - Mice, Inbred C57BL MH - Neurofilament Proteins/genetics/metabolism MH - Prosencephalon/drug effects/*metabolism MH - Proteome/*genetics/metabolism MH - Pyridines/*pharmacology MH - Ribonucleoproteins/genetics/metabolism MH - Schizophrenia/*genetics/metabolism MH - rab GTP-Binding Proteins/genetics/metabolism OTO - NOTNLM OT - FMRP OT - FXS OT - MPEP OT - autism OT - brain OT - mGluR5 OT - schizophrenia EDAT- 2018/09/04 06:00 MHDA- 2020/04/23 06:00 CRDT- 2018/09/04 06:00 PHST- 2018/03/15 00:00 [received] PHST- 2018/08/13 00:00 [revised] PHST- 2018/08/30 00:00 [accepted] PHST- 2018/09/04 06:00 [pubmed] PHST- 2020/04/23 06:00 [medline] PHST- 2018/09/04 06:00 [entrez] AID - 10.1002/syn.22069 [doi] PST - ppublish SO - Synapse. 2019 Jan;73(1):e22069. doi: 10.1002/syn.22069. Epub 2018 Oct 3.