A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms
Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) i...
Ausführliche Beschreibung
Autor*in: |
Lepeta, Katarzyna [verfasserIn] Purzycka, Katarzyna J [verfasserIn] Pachulska‐Wieczorek, Katarzyna [verfasserIn] Mitjans, Marina [verfasserIn] Begemann, Martin [verfasserIn] Vafadari, Behnam [verfasserIn] Bijata, Krystian [verfasserIn] Adamiak, Ryszard W [verfasserIn] Ehrenreich, Hannelore [verfasserIn] Dziembowska, Magdalena [verfasserIn] Kaczmarek, Leszek [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2017 |
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Schlagwörter: |
Fragile X mental retardation protein |
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Anmerkung: |
© The Authors. Published under the terms of the CC BY 4.0 license 2017 |
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Übergeordnetes Werk: |
Enthalten in: EMBO Molecular Medicine - Nature Publishing Group UK, 2023, 9(2017), 8 vom: 16. Juni, Seite 1100-1116 |
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Übergeordnetes Werk: |
volume:9 ; year:2017 ; number:8 ; day:16 ; month:06 ; pages:1100-1116 |
Links: |
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DOI / URN: |
10.15252/emmm.201707723 |
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Katalog-ID: |
SPR057909539 |
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245 | 1 | 0 | |a A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms |
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520 | |a Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. | ||
520 | |a Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. | ||
520 | |a Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. | ||
650 | 4 | |a dendritic spine morphology |7 (dpeaa)DE-He213 | |
650 | 4 | |a Fragile X mental retardation protein |7 (dpeaa)DE-He213 | |
650 | 4 | |a matrix metalloproteinase 9 |7 (dpeaa)DE-He213 | |
650 | 4 | |a phenotype‐based genetic association study |7 (dpeaa)DE-He213 | |
650 | 4 | |a single‐nucleotide polymorphism |7 (dpeaa)DE-He213 | |
700 | 1 | |a Purzycka, Katarzyna J |e verfasserin |4 aut | |
700 | 1 | |a Pachulska‐Wieczorek, Katarzyna |e verfasserin |4 aut | |
700 | 1 | |a Mitjans, Marina |e verfasserin |4 aut | |
700 | 1 | |a Begemann, Martin |e verfasserin |4 aut | |
700 | 1 | |a Vafadari, Behnam |e verfasserin |4 aut | |
700 | 1 | |a Bijata, Krystian |e verfasserin |4 aut | |
700 | 1 | |a Adamiak, Ryszard W |e verfasserin |4 aut | |
700 | 1 | |a Ehrenreich, Hannelore |e verfasserin |4 aut | |
700 | 1 | |a Dziembowska, Magdalena |e verfasserin |4 aut | |
700 | 1 | |a Kaczmarek, Leszek |e verfasserin |0 (orcid)0000-0002-7207-3490 |4 aut | |
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10.15252/emmm.201707723 doi (DE-627)SPR057909539 (SPR)emmm.201707723-e DE-627 ger DE-627 rakwb eng Lepeta, Katarzyna verfasserin aut A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 Purzycka, Katarzyna J verfasserin aut Pachulska‐Wieczorek, Katarzyna verfasserin aut Mitjans, Marina verfasserin aut Begemann, Martin verfasserin aut Vafadari, Behnam verfasserin aut Bijata, Krystian verfasserin aut Adamiak, Ryszard W verfasserin aut Ehrenreich, Hannelore verfasserin aut Dziembowska, Magdalena verfasserin aut Kaczmarek, Leszek verfasserin (orcid)0000-0002-7207-3490 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 9(2017), 8 vom: 16. Juni, Seite 1100-1116 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:9 year:2017 number:8 day:16 month:06 pages:1100-1116 https://dx.doi.org/10.15252/emmm.201707723 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2017 8 16 06 1100-1116 |
spelling |
10.15252/emmm.201707723 doi (DE-627)SPR057909539 (SPR)emmm.201707723-e DE-627 ger DE-627 rakwb eng Lepeta, Katarzyna verfasserin aut A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 Purzycka, Katarzyna J verfasserin aut Pachulska‐Wieczorek, Katarzyna verfasserin aut Mitjans, Marina verfasserin aut Begemann, Martin verfasserin aut Vafadari, Behnam verfasserin aut Bijata, Krystian verfasserin aut Adamiak, Ryszard W verfasserin aut Ehrenreich, Hannelore verfasserin aut Dziembowska, Magdalena verfasserin aut Kaczmarek, Leszek verfasserin (orcid)0000-0002-7207-3490 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 9(2017), 8 vom: 16. Juni, Seite 1100-1116 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:9 year:2017 number:8 day:16 month:06 pages:1100-1116 https://dx.doi.org/10.15252/emmm.201707723 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2017 8 16 06 1100-1116 |
allfields_unstemmed |
10.15252/emmm.201707723 doi (DE-627)SPR057909539 (SPR)emmm.201707723-e DE-627 ger DE-627 rakwb eng Lepeta, Katarzyna verfasserin aut A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 Purzycka, Katarzyna J verfasserin aut Pachulska‐Wieczorek, Katarzyna verfasserin aut Mitjans, Marina verfasserin aut Begemann, Martin verfasserin aut Vafadari, Behnam verfasserin aut Bijata, Krystian verfasserin aut Adamiak, Ryszard W verfasserin aut Ehrenreich, Hannelore verfasserin aut Dziembowska, Magdalena verfasserin aut Kaczmarek, Leszek verfasserin (orcid)0000-0002-7207-3490 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 9(2017), 8 vom: 16. Juni, Seite 1100-1116 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:9 year:2017 number:8 day:16 month:06 pages:1100-1116 https://dx.doi.org/10.15252/emmm.201707723 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2017 8 16 06 1100-1116 |
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10.15252/emmm.201707723 doi (DE-627)SPR057909539 (SPR)emmm.201707723-e DE-627 ger DE-627 rakwb eng Lepeta, Katarzyna verfasserin aut A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 Purzycka, Katarzyna J verfasserin aut Pachulska‐Wieczorek, Katarzyna verfasserin aut Mitjans, Marina verfasserin aut Begemann, Martin verfasserin aut Vafadari, Behnam verfasserin aut Bijata, Krystian verfasserin aut Adamiak, Ryszard W verfasserin aut Ehrenreich, Hannelore verfasserin aut Dziembowska, Magdalena verfasserin aut Kaczmarek, Leszek verfasserin (orcid)0000-0002-7207-3490 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 9(2017), 8 vom: 16. Juni, Seite 1100-1116 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:9 year:2017 number:8 day:16 month:06 pages:1100-1116 https://dx.doi.org/10.15252/emmm.201707723 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2017 8 16 06 1100-1116 |
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10.15252/emmm.201707723 doi (DE-627)SPR057909539 (SPR)emmm.201707723-e DE-627 ger DE-627 rakwb eng Lepeta, Katarzyna verfasserin aut A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Authors. Published under the terms of the CC BY 4.0 license 2017 Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 Purzycka, Katarzyna J verfasserin aut Pachulska‐Wieczorek, Katarzyna verfasserin aut Mitjans, Marina verfasserin aut Begemann, Martin verfasserin aut Vafadari, Behnam verfasserin aut Bijata, Krystian verfasserin aut Adamiak, Ryszard W verfasserin aut Ehrenreich, Hannelore verfasserin aut Dziembowska, Magdalena verfasserin aut Kaczmarek, Leszek verfasserin (orcid)0000-0002-7207-3490 aut Enthalten in EMBO Molecular Medicine Nature Publishing Group UK, 2023 9(2017), 8 vom: 16. Juni, Seite 1100-1116 (DE-627)594772761 (DE-600)2485479-7 1757-4684 nnns volume:9 year:2017 number:8 day:16 month:06 pages:1100-1116 https://dx.doi.org/10.15252/emmm.201707723 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 9 2017 8 16 06 1100-1116 |
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Lepeta, Katarzyna @@aut@@ Purzycka, Katarzyna J @@aut@@ Pachulska‐Wieczorek, Katarzyna @@aut@@ Mitjans, Marina @@aut@@ Begemann, Martin @@aut@@ Vafadari, Behnam @@aut@@ Bijata, Krystian @@aut@@ Adamiak, Ryszard W @@aut@@ Ehrenreich, Hannelore @@aut@@ Dziembowska, Magdalena @@aut@@ Kaczmarek, Leszek @@aut@@ |
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We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. 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A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms dendritic spine morphology (dpeaa)DE-He213 Fragile X mental retardation protein (dpeaa)DE-He213 matrix metalloproteinase 9 (dpeaa)DE-He213 phenotype‐based genetic association study (dpeaa)DE-He213 single‐nucleotide polymorphism (dpeaa)DE-He213 |
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Lepeta, Katarzyna Purzycka, Katarzyna J Pachulska‐Wieczorek, Katarzyna Mitjans, Marina Begemann, Martin Vafadari, Behnam Bijata, Krystian Adamiak, Ryszard W Ehrenreich, Hannelore Dziembowska, Magdalena Kaczmarek, Leszek |
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a normal genetic variation modulates synaptic mmp‐9 protein levels and the severity of schizophrenia symptoms |
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A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms |
abstract |
Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
abstractGer |
Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
abstract_unstemmed |
Abstract Matrix metalloproteinase 9 (MMP‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype‐based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP‐9 rs20544 C/T single‐nucleotide polymorphism (SNP) located in the 3′untranslated region (UTR) and the severity of a chronic delusional syndrome. In cultured neurons, the rs20544 SNP influenced synaptic MMP‐9 activity and the morphology of dendritic spines. We demonstrated that Fragile X mental retardation protein (FMRP) bound the MMP‐9 3′UTR. We also found dramatic changes in RNA structure folding and alterations in the affinity of FMRP for MMP‐9 RNA, depending on the SNP variant. Finally, we observed greater sensitivity to psychosis‐related locomotor hyperactivity in Mmp‐9 heterozygous mice. We propose a novel mechanism that involves MMP‐9‐dependent changes in dendritic spine morphology and the pathophysiology of schizophrenia, providing the first mechanistic insights into the way in which the single base change in the MMP‐9 gene (rs20544) influences gene function and results in phenotypic changes observed in schizophrenia patients. Synopsis A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity. Graphical Abstract A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients. © The Authors. Published under the terms of the CC BY 4.0 license 2017 |
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title_short |
A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms |
url |
https://dx.doi.org/10.15252/emmm.201707723 |
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Purzycka, Katarzyna J Pachulska‐Wieczorek, Katarzyna Mitjans, Marina Begemann, Martin Vafadari, Behnam Bijata, Krystian Adamiak, Ryszard W Ehrenreich, Hannelore Dziembowska, Magdalena Kaczmarek, Leszek |
author2Str |
Purzycka, Katarzyna J Pachulska‐Wieczorek, Katarzyna Mitjans, Marina Begemann, Martin Vafadari, Behnam Bijata, Krystian Adamiak, Ryszard W Ehrenreich, Hannelore Dziembowska, Magdalena Kaczmarek, Leszek |
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doi_str |
10.15252/emmm.201707723 |
up_date |
2024-10-19T04:52:28.210Z |
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|
score |
7.39818 |