Multiple Early-life Seizures Alter Neonatal Communicative Behavior in Fmr1 Knockout Mice

Date
2021
Authors
Nguyen, Phuoc
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Abstract

Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and a significant contributor to Autism spectrum disorder. In addition to autistic-like phenotypes, individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how FMR1 germline mutation impacts neonatal communicative behavior in the FXS mouse model, both with and without early-life seizures (ELSs). On postnatal day (PD) 7 through PD11, we administered 3 flurothyl seizures to both Fmr1 KO and wild type mice. On PD12, all pups were temporarily isolated from their home cage and USVs were recorded. Significant alterations were found in both spectral and temporal measurements across seizure groups. We found that induction of seizures across PD7–11 resulted in increased frequency of USVs produced (P < 0.05), longer duration (P < 0.05), and cumulative duration (P < 0.05) in both genotypes. Overall, this study provides evidence that magnitude of communication impairment in FXS mice is significantly impacted by seizure frequency load early in development.

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Keywords
Early-life seizures., Fragile X Syndrome., Vocalization., Flurothyl., Critical period.
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