Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat
Fragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the developm...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00384/full |
| _version_ | 1818507499191402496 |
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| author | Roman Smidak Fernando J. Sialana Martina Kristofova Tamara Stojanovic Dragana Rajcic Jovana Malikovic Daniel D. Feyissa Volker Korz Harald Hoeger Judit Wackerlig Diana Mechtcheriakova Gert Lubec Gert Lubec |
| author_facet | Roman Smidak Fernando J. Sialana Martina Kristofova Tamara Stojanovic Dragana Rajcic Jovana Malikovic Daniel D. Feyissa Volker Korz Harald Hoeger Judit Wackerlig Diana Mechtcheriakova Gert Lubec Gert Lubec |
| author_sort | Roman Smidak |
| collection | DOAJ |
| description | Fragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS) that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG) from young (17 weeks) and aging (22 months) Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM) and CUG-BP, Elav-like (CELF) family, and YTH N(6)-methyladenosine RNA-binding proteins (YTHDF). The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process. |
| first_indexed | 2024-12-10T22:19:11Z |
| format | Article |
| id | doaj.art-603a42672e224982b083a16070815c71 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-10T22:19:11Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-603a42672e224982b083a16070815c712022-12-22T01:31:22ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652017-11-01910.3389/fnagi.2017.00384313665Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley RatRoman Smidak0Fernando J. Sialana1Martina Kristofova2Tamara Stojanovic3Dragana Rajcic4Jovana Malikovic5Daniel D. Feyissa6Volker Korz7Harald Hoeger8Judit Wackerlig9Diana Mechtcheriakova10Gert Lubec11Gert Lubec12Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaCore Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Vienna, AustriaCore Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaDepartment of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, AustriaNeuroproteomics, Paracelsus Private Medical University, Salzburg, AustriaFragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS) that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG) from young (17 weeks) and aging (22 months) Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM) and CUG-BP, Elav-like (CELF) family, and YTH N(6)-methyladenosine RNA-binding proteins (YTHDF). The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.http://journal.frontiersin.org/article/10.3389/fnagi.2017.00384/fullFragile X syndromeFragile X mental retardation proteinbrain agingdentate gyrusproteomicsRNA-binding protein |
| spellingShingle | Roman Smidak Fernando J. Sialana Martina Kristofova Tamara Stojanovic Dragana Rajcic Jovana Malikovic Daniel D. Feyissa Volker Korz Harald Hoeger Judit Wackerlig Diana Mechtcheriakova Gert Lubec Gert Lubec Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat Frontiers in Aging Neuroscience Fragile X syndrome Fragile X mental retardation protein brain aging dentate gyrus proteomics RNA-binding protein |
| title | Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat |
| title_full | Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat |
| title_fullStr | Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat |
| title_full_unstemmed | Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat |
| title_short | Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat |
| title_sort | reduced levels of the synaptic functional regulator fmrp in dentate gyrus of the aging sprague dawley rat |
| topic | Fragile X syndrome Fragile X mental retardation protein brain aging dentate gyrus proteomics RNA-binding protein |
| url | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00384/full |
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