Cerebellar contribution to autism-relevant behaviors in fragile X syndrome models.
Cell Rep
; 42(12): 113533, 2023 12 26.
Article
in En
| MEDLINE
| ID: mdl-38048226
ABSTRACT
Cerebellar dysfunction has been linked to autism spectrum disorders (ASDs). Although cerebellar pathology has been observed in individuals with fragile X syndrome (FXS) and in mouse models of the disorder, a cerebellar functional contribution to ASD-relevant behaviors in FXS has yet to be fully characterized. In this study, we demonstrate a critical cerebellar role for Fmr1 (fragile X messenger ribonucleoprotein 1) in ASD-relevant behaviors. First, we identify reduced social behaviors, sensory hypersensitivity, and cerebellar dysfunction, with loss of cerebellar Fmr1. We then demonstrate that cerebellar-specific expression of Fmr1 is sufficient to impact social, sensory, cerebellar dysfunction, and cerebro-cortical hyperexcitability phenotypes observed in global Fmr1 mutants. Moreover, we demonstrate that targeting the ASD-implicated cerebellar region Crus1 ameliorates behaviors in both cerebellar-specific and global Fmr1 mutants. Together, these results demonstrate a critical role for the cerebellar contribution to FXS-related behaviors, with implications for future therapeutic strategies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autistic Disorder
/
Cerebellar Diseases
/
Autism Spectrum Disorder
/
Fragile X Syndrome
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2023
Document type:
Article
Affiliation country: