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 Δexon 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 Δexon 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 Δexon 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.

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. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 12:1(2022), pp. 1-15. [10.1038/s41598-022-26986-2]

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

Antonia Manduca
Writing – Original Draft Preparation
;
Alessandro Rava;Valeria Buzzelli;Filippo Galli;Alessandro Soluri;Viviana Trezza
2022

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 Δexon 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 Δexon 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 Δexon 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.
2022
fmr1; dopamine; spect
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 12:1(2022), pp. 1-15. [10.1038/s41598-022-26986-2]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1664436
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