FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability
Abstract Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are m...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26986-2 |
| _version_ | 1797973671485112320 |
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| author | Annunziata D’Elia Sara Schiavi Antonia Manduca Alessandro Rava Valeria Buzzelli Fabrizio Ascone Tiziana Orsini Sabrina Putti Andrea Soluri Filippo Galli Alessandro Soluri Maurizio Mattei Rosella Cicconi Roberto Massari Viviana Trezza |
| author_facet | Annunziata D’Elia Sara Schiavi Antonia Manduca Alessandro Rava Valeria Buzzelli Fabrizio Ascone Tiziana Orsini Sabrina Putti Andrea Soluri Filippo Galli Alessandro Soluri Maurizio Mattei Rosella Cicconi Roberto Massari Viviana Trezza |
| author_sort | Annunziata D’Elia |
| collection | DOAJ |
| description | Abstract Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 Δ exon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 Δ exon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 Δ exon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses. |
| first_indexed | 2024-04-11T04:08:00Z |
| format | Article |
| id | doaj.art-f43dc9cee6904ebbb49b46ea22ad70a6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T04:08:00Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f43dc9cee6904ebbb49b46ea22ad70a62023-01-01T12:18:35ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-26986-2FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availabilityAnnunziata D’Elia0Sara Schiavi1Antonia Manduca2Alessandro Rava3Valeria Buzzelli4Fabrizio Ascone5Tiziana Orsini6Sabrina Putti7Andrea Soluri8Filippo Galli9Alessandro Soluri10Maurizio Mattei11Rosella Cicconi12Roberto Massari13Viviana Trezza14Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityDepartment of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityDepartment of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityDepartment of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityDepartment of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityInstitute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of RomeInstitute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Department of Biology and Centro di Servizi Interdipartimentale-Stazione per la Tecnologia Animale, “Tor Vergata” UniversityDepartment of Biology and Centro di Servizi Interdipartimentale-Stazione per la Tecnologia Animale, “Tor Vergata” UniversityInstitute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR)Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre UniversityAbstract Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 Δ exon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 Δ exon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 Δ exon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses.https://doi.org/10.1038/s41598-022-26986-2 |
| spellingShingle | Annunziata D’Elia Sara Schiavi Antonia Manduca Alessandro Rava Valeria Buzzelli Fabrizio Ascone Tiziana Orsini Sabrina Putti Andrea Soluri Filippo Galli Alessandro Soluri Maurizio Mattei Rosella Cicconi Roberto Massari Viviana Trezza FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability Scientific Reports |
| title | FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| title_full | FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| title_fullStr | FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| title_full_unstemmed | FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| title_short | FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| title_sort | fmr1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability |
| url | https://doi.org/10.1038/s41598-022-26986-2 |
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