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
| Autor: | S. Hossein Fatemi, LeeAnn Higgins, Todd W. Markowski, Timothy D. Folsom, Timothy J. Griffin |
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| Rok vydání: | 2018 |
| Předmět: |
HNRNPC
Heterogeneous nuclear ribonucleoprotein Proteome Pyridines Heterogeneous ribonucleoprotein particle Fragile X Mental Retardation Protein Mice 03 medical and health sciences Cellular and Molecular Neuroscience GAP-43 Protein Prosencephalon 0302 clinical medicine 2' 3'-Cyclic Nucleotide 3'-Phosphodiesterase Neurofilament Proteins medicine Animals Gap-43 protein 030304 developmental biology 0303 health sciences biology Chemistry medicine.disease Molecular biology FMR1 3. Good health Mice Inbred C57BL Fragile X syndrome Excitatory Amino Acid Transporter 2 Ribonucleoproteins rab GTP-Binding Proteins Knockout mouse Schizophrenia biology.protein Rab Excitatory Amino Acid Antagonists Gene Deletion 030217 neurology & neurosurgery |
| Zdroj: | Synapse. 73 |
| ISSN: | 1098-2396 0887-4476 |
| DOI: | 10.1002/syn.22069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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