Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice
Summary: Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviors (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009129 |
| _version_ | 1797731118431076352 |
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| author | Francesco Longo Sameer Aryal Paul G. Anastasiades Marta Maltese Corey Baimel Federica Albanese Joanna Tabor Jeffrey D. Zhu Mauricio M. Oliveira Denise Gastaldo Claudia Bagni Emanuela Santini Nicolas X. Tritsch Adam G. Carter Eric Klann |
| author_facet | Francesco Longo Sameer Aryal Paul G. Anastasiades Marta Maltese Corey Baimel Federica Albanese Joanna Tabor Jeffrey D. Zhu Mauricio M. Oliveira Denise Gastaldo Claudia Bagni Emanuela Santini Nicolas X. Tritsch Adam G. Carter Eric Klann |
| author_sort | Francesco Longo |
| collection | DOAJ |
| description | Summary: Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviors (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissect the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. Here, we report that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum reveals differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings uncover a cell-type-specific impact of the loss of fragile X messenger ribonucleoprotein (FMRP) on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS. |
| first_indexed | 2024-03-12T11:54:09Z |
| format | Article |
| id | doaj.art-dc43b9ea499f4df290879ca6923d0caf |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:54:09Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-dc43b9ea499f4df290879ca6923d0caf2023-08-31T05:02:07ZengElsevierCell Reports2211-12472023-08-01428112901Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model miceFrancesco Longo0Sameer Aryal1Paul G. Anastasiades2Marta Maltese3Corey Baimel4Federica Albanese5Joanna Tabor6Jeffrey D. Zhu7Mauricio M. Oliveira8Denise Gastaldo9Claudia Bagni10Emanuela Santini11Nicolas X. Tritsch12Adam G. Carter13Eric Klann14Center for Neural Science, New York University, New York, NY 10003, USA; Institute for Neuroscience and Physiology, University of Gothenburg, 40530 Gothenburg, Sweden; Sackler Institute of Graduate Biomedical Sciences, NYU School of Medicine, New York, NY 10016, USACenter for Neural Science, New York University, New York, NY 10003, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY 10016, USACenter for Neural Science, New York University, New York, NY 10003, USAFresco Institute for Parkinson’s and Movement Disorders, New York University Langone Health, New York, NY 10016, USA; Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, SwitzerlandCenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USADepartment of Biomedicine and Prevention, University of Rome “Tor Vergata,” 1005 Rome, ItalyDepartment of Biomedicine and Prevention, University of Rome “Tor Vergata,” 1005 Rome, ItalyCenter for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience, Biomedicum, Karolinska Institute, 171 77 Stockholm, SwedenNYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY 10016, USA; Fresco Institute for Parkinson’s and Movement Disorders, New York University Langone Health, New York, NY 10016, USACenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY 10016, USA; Corresponding authorSummary: Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviors (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissect the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. Here, we report that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum reveals differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings uncover a cell-type-specific impact of the loss of fragile X messenger ribonucleoprotein (FMRP) on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS.http://www.sciencedirect.com/science/article/pii/S2211124723009129CP: Neuroscience |
| spellingShingle | Francesco Longo Sameer Aryal Paul G. Anastasiades Marta Maltese Corey Baimel Federica Albanese Joanna Tabor Jeffrey D. Zhu Mauricio M. Oliveira Denise Gastaldo Claudia Bagni Emanuela Santini Nicolas X. Tritsch Adam G. Carter Eric Klann Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice Cell Reports CP: Neuroscience |
| title | Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice |
| title_full | Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice |
| title_fullStr | Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice |
| title_full_unstemmed | Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice |
| title_short | Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice |
| title_sort | cell type specific disruption of cortico striatal circuitry drives repetitive patterns of behavior in fragile x syndrome model mice |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723009129 |
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