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512 Odorant exposure decreases mortality in a Dravet Syndrome mouse model
Published online by Cambridge University Press: 24 April 2023
Abstract
OBJECTIVES/GOALS: Our goal was to explore the actions of odorants on mortality and seizures in a DS mouse model (scn1a+/-), which have spontaneous seizures and high rate of SUDEP. We hypothesize that odorants that have actions on olfactory->;extended amygdala pathways will decrease SUDEP, potentially through attenuation of neuronal activation in the extended amygdala. METHODS/STUDY POPULATION: Dravet syndrome mice (heterozygous scn1a+/- ) were exposed for at least eight hours a day to either 2-phenylethanol (2PE, rose odor ), lemon extract, or vehicle odorant in group housed cages. This was repeated daily for 15 days starting at postnatal day 20/21. Mortality in each group was recorded. A subset of 2PE-exposed animals had an extended washout period following odorant exposure to continue to determine the long-term effect of odorant exposure on mortality. RESULTS/ANTICIPATED RESULTS: Our preliminary results show a strong trend for decreased mortality in the 2PE-exposed group (16.1% mortality (n=31) vs 38.5% mortality in vehicle control (n=26), p=0.06, Barnard’s test). Survival analyses show similar results (p=0.056 Kaplan-Meier curve, p=0.046 when removing those animals that died before completing day one of exposure). The lemon scent-exposed animals had a non-significant increase in mortality compared to controls from our preliminary experiments (50% mortality, n=8). Overall, these results suggest that mortality effect is dependent on specific odorants and that this effect is transient. DISCUSSION/SIGNIFICANCE: Our preliminary data support that odorant exposure can decrease mortality in a Dravet Syndrome mouse model, suggesting that more work to determine the mechanism of action and circuitry involved may illuminate new targets and therapies for preventing SUDEP in epilepsy patients.
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- This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
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- © The Author(s), 2023. The Association for Clinical and Translational Science