Effects of a Novel, Non-Toxic Histone Deacetylase Inhibitor on Memory Formation in Mice

Olivia Dye, “Effects of a Novel, Non-Toxic Histone Deacetylase Inhibitor on Memory Formation in Mice”
Mentors: Karyn Frick & Sarah Beamish, Psychology

As researchers make strides to understand how the brain and memory function, memory formation continues to have many unknowns. Chromatin remodeling through epigenetic modifications, such as histone acetylation, promotes successful formation of long-term memories by increasing levels of gene expression. Research demonstrates that histone deacetylase inhibitors (HDACi) improve memory by preventing the deacetylation of core histone proteins and allowing transcriptional machinery to increase access to open chromatin. HDACi are a promising therapeutic target for memory decline, however, the memory enhancing effects of existing HDACi are precluded by their high toxicity and unwanted solubility. In collaboration with the Chemistry and Biology Departments at UWM, we have developed a novel brain-penetrant HDACi compound, Cpd1’, that shows no evidence of toxicity. Data collected from our lab indicates that Cpd1’ is capable of enhancing spatial memory in mice. However, it remains unclear the extent to which Cpd1’ modifies levels of histone acetylation in the brain. The goal of this work is to determine whether Cpd1’ modifies histone acetylation levels in a time-dependent manner in the dorsal hippocampus (DH). Mice received an intraperitoneal injection of negative control (100% DMSO), positive HDACi control sodium butyrate (0.6 g/kg NaBu), or one of three doses of Cpd1′ (20,30,40 µg/g), and the DH was dissected 1 hr later. DH tissue was then homogenized so that histones were extracted, and any posttranslational modifications were kept intact. Here we present Western blot data of histone acetylation changes in the DH after 1 hr treatment. Collectively, this work represents a step forward in providing safer therapeutic treatments that can be used to treat memory decline.

 

Comments

  1. Olivia,
    Great job on your presentation. Your slides and delivery are excellent (e.g., clear, loud voice that is animated, which helps maintain my interest). This research is complex with important implications, and you do a very good job explaining the concepts and your study. I’m amazed you are an undergraduate–nice work!

    While I understand much of what you discuss, I recommend working on how you might translate the information for an uninformed audience so they might connect with it and recognize its value. On a related point, I’d love to see you address/make clear how this research fits into the larger body of scholarship and what is the main take-home message from your findings.

    Overall, EXCELLENT job, and good luck with your future work!
    Cheers to health,
    Dr. Erin Parcell (Communication)

  2. Olivia,
    I echo everything said above- excellent work, and very clearly presented. I’m impressed with the video, which seems above and beyond the actual work in the lab. Very polished and quite clear.

    All the best with your future research!
    Jim Wasley (Architecture)

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