Changes in Electroencephalography signals in a juvenile female Fragile X Syndrome mouse model

Abstract

BackgroundFragile X syndrome (FXS) is the leading monogenic cause of Autism. Seizures, hyperactivity, and anxiety are common symptoms of FXS. No broadly effective support option currently exists for FXS, and drug development has suffered many failures in clinical trials based on promising preclinical findings. Thus, effective translational biomarkers of treatment outcomes are needed. Recently electroencephalography (EEG) has been proposed as a translational biomarker in FXS. Being X-linked, FXS is more prevalent in males than females, and there exist significant phenotype differences between males and females with FXS. Recent studies involving male FXS participants and rodent models have identified an increase in absolute gamma EEG power, while alpha power is found to be either decreased or unchanged. However, there is not enough research on female FXS patients or models. In addition, studying EEG activity in young FXS patients or rodent models is crucial for better understanding of the disorder’s effects on brain development.Therefore, we aim to compare EEG signal between wild-type (WT) andfmr1knockout (KO) female mice at the juvenile stage.MethodsFrontal-parietal differential EEG was recorded using a stand-alone Open-Source Electrophysiology Recording system for Rodents (OSERR). EEG activity was recorded in three different conditions: a) in the subject’s home cage and in the arenas for b) light and dark test and C) open field test. Absolute and relative EEG power as well as phase-amplitude coupling were computed for each condition.ResultsIn our study, we found absolute alpha, beta, and gamma EEG power is increased in femalefmr1 KOmice compared to WT controls at the juvenile age. Alongside, relative theta power is decreased in thefmr1 KOfemales. Furthermore, phase-amplitude coupling is increased in thefmr1 KOfemales.Discussion and ConclusionComparing to the reported changes in EEG signal in male FXS patients and models, our results indicated the presence of sex-based differences in EEG phenotypes at the juvenile stage. Collectively, these findings suggest that sex is an importance factor to consider in utilizing EEG as a translational biomarker in FXS.