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FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

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...

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Autores principales: D’Elia, Annunziata, Schiavi, Sara, Manduca, Antonia, Rava, Alessandro, Buzzelli, Valeria, Ascone, Fabrizio, Orsini, Tiziana, Putti, Sabrina, Soluri, Andrea, Galli, Filippo, Soluri, Alessandro, Mattei, Maurizio, Cicconi, Rosella, Massari, Roberto, Trezza, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800572/
https://www.ncbi.nlm.nih.gov/pubmed/36581671
http://dx.doi.org/10.1038/s41598-022-26986-2
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author D’Elia, Annunziata
Schiavi, Sara
Manduca, Antonia
Rava, Alessandro
Buzzelli, Valeria
Ascone, Fabrizio
Orsini, Tiziana
Putti, Sabrina
Soluri, Andrea
Galli, Filippo
Soluri, Alessandro
Mattei, Maurizio
Cicconi, Rosella
Massari, Roberto
Trezza, Viviana
author_facet D’Elia, Annunziata
Schiavi, Sara
Manduca, Antonia
Rava, Alessandro
Buzzelli, Valeria
Ascone, Fabrizio
Orsini, Tiziana
Putti, Sabrina
Soluri, Andrea
Galli, Filippo
Soluri, Alessandro
Mattei, Maurizio
Cicconi, Rosella
Massari, Roberto
Trezza, Viviana
author_sort D’Elia, Annunziata
collection PubMed
description 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.
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spelling pubmed-98005722022-12-31 FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability D’Elia, Annunziata Schiavi, Sara Manduca, Antonia Rava, Alessandro Buzzelli, Valeria Ascone, Fabrizio Orsini, Tiziana Putti, Sabrina Soluri, Andrea Galli, Filippo Soluri, Alessandro Mattei, Maurizio Cicconi, Rosella Massari, Roberto Trezza, Viviana Sci Rep Article 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. Nature Publishing Group UK 2022-12-29 /pmc/articles/PMC9800572/ /pubmed/36581671 http://dx.doi.org/10.1038/s41598-022-26986-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
D’Elia, Annunziata
Schiavi, Sara
Manduca, Antonia
Rava, Alessandro
Buzzelli, Valeria
Ascone, Fabrizio
Orsini, Tiziana
Putti, Sabrina
Soluri, Andrea
Galli, Filippo
Soluri, Alessandro
Mattei, Maurizio
Cicconi, Rosella
Massari, Roberto
Trezza, Viviana
FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800572/
https://www.ncbi.nlm.nih.gov/pubmed/36581671
http://dx.doi.org/10.1038/s41598-022-26986-2
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