Scheduled feeding improves behavioral outcomes and reduces inflammation in a mouse model of Fragile X syndrome

Published: Feb. 21, 2025

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the abnormal expansion of CGG repeats in fragile mental retardation 1 (FMR1) gene. Many FXS patients experience sleep disruptions, and we sought to explore these symptoms along with possible benefits scheduled feeding intervention using Fmr1 knockout (KO) mouse model. These mutants displayed clear evidence for circadian disturbances including delay onset fragmented activity rhythms increases cycle-to-cycle variability. Importantly, KO mice exhibited deficits their behavioral response light reduced masking, longer time resetting shifts Light-Dark cycle, altered synchronization skeleton photoperiod lower magnitude light-induced phase rhythms. Investigation retinal input surprachiasmatic nucleus (SCN) neurotracer cholera toxin (β subunit) quantification light-evoked cFos expression SCN revealed an innervation KO, providing mechanistic explanation observed deficits. Interestingly, disruptions social repetitive behaviors correlated duration fragmentation. Understanding nature deficits, decided apply regimen (6-hr/18-hr feed/fast cycle) as circadian-based strategy boast independently light. This significantly improved mutants. Strikingly, ameliorated interactions well levels Interferon-gamma Interleukin-12 mutants, suggesting that timed eating may be effective way lessen inflammation. Collectively, this work adds support efforts develop based interventions help disorders.

Language: Английский

Scheduled feeding improves behavioral outcomes and reduces inflammation in a mouse model of Fragile X syndrome

Published: Feb. 21, 2025

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the abnormal expansion of CGG repeats in fragile mental retardation 1 (FMR1) gene. Many FXS patients experience sleep disruptions, and we sought to explore these symptoms along with possible benefits scheduled feeding intervention using Fmr1 knockout (KO) mouse model. These mutants displayed clear evidence for circadian disturbances including delay onset fragmented activity rhythms increases cycle-to-cycle variability. Importantly, KO mice exhibited deficits their behavioral response light reduced masking, longer time resetting shifts Light-Dark cycle, altered synchronization skeleton photoperiod lower magnitude light-induced phase rhythms. Investigation retinal input surprachiasmatic nucleus (SCN) neurotracer cholera toxin (β subunit) quantification light-evoked cFos expression SCN revealed an innervation KO, providing mechanistic explanation observed deficits. Interestingly, disruptions social repetitive behaviors correlated duration fragmentation. Understanding nature deficits, decided apply regimen (6-hr/18-hr feed/fast cycle) as circadian-based strategy boast independently light. This significantly improved mutants. Strikingly, ameliorated interactions well levels Interferon-gamma Interleukin-12 mutants, suggesting that timed eating may be effective way lessen inflammation. Collectively, this work adds support efforts develop based interventions help disorders.

Language: Английский

Scheduled feeding improves behavioral outcomes and reduces inflammation in a mouse model of Fragile X syndrome

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Abstract Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the abnormal expansion of CGG repeats in fragile mental retardation 1 (FMR1) gene. Many FXS patients experience sleep disruptions, and we sought to explore these symptoms along with possible benefits scheduled feeding intervention using Fmr1 knockout (KO) mouse model. These mutants displayed clear evidence for circadian disturbances including delay onset fragmented activity rhythms increases cycle-to-cycle variability. The KO mice exhibited deficits their behavioral response light reduced masking, longer time resetting shifts LD cycle, altered synchronization skeleton photoperiod lower magnitude light-induced phase rhythms. Investigation retinal input surprachiasmatic nucleus (SCN) neurotracer cholera toxin (β subunit) quantification light-evoked cFos expression SCN revealed an innervation KO, providing mechanistic explanation observed deficits. Interestingly, disruptions social repetitive behavior correlated duration fragmentation. Understanding nature deficits, decided apply regimen (6-hr/18-hr feed/fast cycle) as circadian-based strategy boast independently light. This significantly improved mutants. Strikingly, ameliorated interactions behaviors well levels Interferon-gamma Interleukin-12 mutants, suggesting that timed eating may be effective way reduce inflammation. Collectively, this work adds support efforts develop based interventions help disorders.

Language: Английский