Developmental Acoustic Exposure as a Novel Approach to Treat Fragile X Syndrome
Abstract
The main goal of the proposed studies was to test the hypothesis that a combination of sound exposure and minocycline treatment provided to the mouse model of Fragile X Syndrome (FXS), will cause a long lasting benefit in terms of sensory hypersensitivity and behaviors as adults. This project addresses a major gap in the autism literature on when the appropriate treatment window is. The first year of the project period has been highly productive, despite the loss of a significant amount of time and resources to the pandemic-related shut-downs of our university. We have published five papers and two reviews in 2020 from this project. In Kulinich et al (2020), we showed the beneficial effects of early life 5Hz repetition rate sound exposure on hyperexcitability correlates in Fmr1 KO mice. This is one of the major aims of the project. In Lovelace et al (2020), we showed that minocycline treatment in adult mice has an impact on sound evoked EEG responses, but not resting EEG compared to vehicle treatment. In Pirbhoy et al (2020), we showed that a more specific inhibitor (SB-3CT) that works like minocycline to reduce matrix metalloprotease-9 (MMP9) given to developing mice (~P22) works to reduce EEG phenotypes, reverses inhibitory cell phenotypes and improves behaviors even with an acute injection. In Jonak et al (2020), we used a state-of-the-art 30 channel multielectrode array (MEA) system to record EEGs from mouse skull and showed regional differences in EEG phenotypes in adults. In Ngueyn et al (2020), we showed that auditory hypersensitivity correlates are found in the P21-P34 window. These papers provide the foundation for the current grant in testing the same phenotypes following sound exposure and minocycline. We have also analyzed pilot data in the reporting year to show that in the adults, peripheral cochlear function is not different between WT and KO mice. These indicate central auditory processing changes underlie abnormalities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1110110
Entities
People
- Iryna M Ethell
- Khaleel A. Razak
Organizations
- University of California Regents