Department or Program

Neuroscience

Abstract

Previous findings point to a consensus that altering DNA methylation in neurons involved in neuroplasticity circuits is necessary for memory formation2-4. The central hypothesis is that learning experience forms memory for later retrieval via DNA methylation. Two families of epigenetic regulators are investigated. TET dioxygenases detect and oxidize 5-methylcytosine in double-stranded DNA and demethylate DNA5-6. TCF4 also regulates the methylome. It is crucial to neurotypical cognition, as exemplified in Pitt-Hopkins Syndrome (PTHS), where haploinsufficiency of TCF4 results in severe learning deficit, hyperventilation and in some cases epilepsy7-8. To test if decreasing the level of TET enzymatic activity enhances memory and rescues cognition in PTHS models, Tet1 Tcf4 DKO, Tet2 KD and Tet2 conditional KO murine cohorts undergo behavioral assessments. They then donate their hippocampi for totalRNA, polyA+ RNA and whole genome bisulfite sequencing to validate that enhanced associative and spatial memory is linked to increased DNA methylation. Additionally, the memory-rescuing effect of knocking in Tcf4 is currently under investigation using an LSL-Tcf4 cohort. Data analysis is conducted in Prism using unpaired t-test, one-way and two-way ANOVA. Studying regulators of mnemogenic methyl marks further resolves the mechanisms of memory on the molecular level and provides insight into the development of neuro-epigenetic therapies.

Level of Access

Open Access

First Advisor

Kennedy, Andrew

Date of Graduation

5-2019

Degree Name

Bachelor of Science

Number of Pages

120

Download

Embargoed

Open Access

Available to all.

Share

COinS