Cerebellar contribution to autism-relevant behaviors in fragile X syndrome models.

Autor:	Gibson JM; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Vazquez AH; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Yamashiro K; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Jakkamsetti V; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Ren C; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Lei K; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Dentel B; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Pascual JM; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Tsai PT; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: peter.tsai@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Dec 26; Vol. 42 (12), pp. 113533. Date of Electronic Publication: 2023 Dec 03.
DOI:	10.1016/j.celrep.2023.113533
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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