Material Type  

 학위논문

 

0015491471

Date and Time of Latest Transaction  

20200217181259

ISBN  

9781085791878

DDC  

615.9

Author  

Sanchez, Richard G.

Title/Author  

The Influence of O-GlcNAcylation on DNA 5-Hydroxymethylation in The Epileptic Hippocampus

Publish Info  

[Sl] : The University of Alabama at Birmingham, 2019

Publish Info  

Ann Arbor : ProQuest Dissertations & Theses, 2019

Material Info  

304 p

General Note  

Source: Dissertations Abstracts International, Volume: 81-04, Section: B.

General Note  

Advisor: Lubin, Farah D.

학위논문주기  

Thesis (Ph.D.)--The University of Alabama at Birmingham, 2019.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Abstracts/Etc  

요약Epilepsy is a neurological disorder that affects roughly 3 million Americans and 65 million individuals worldwide. Although there are several known causes of epilepsy, little is understood about the development of epilepsy or epileptogenesis. What has been observed through multiple studies of epilepsy is an alteration of the proteomic profile, along with a distinct change in post-translational modifications (PTM). Studies have focused on phosphorylation and a variety of kinases that are upregulated during epilepsy with little clinical translation. This dissertation investigates O-GlcNAcylation, a PTM that is highly intertwined with the cellular metabolism, and its epigenetic effects on gene expression via 5-hydroxymethylcytosine (5hmC) expression in the epileptic hippocampus. We found that in epilepsy global O-GlcNAcylation is downregulated, as well as global 5hmC. Furthermore, there were profound changes decreases in seizures, seizure duration, and severity when O-GlcNAcylation was promoted in epileptic animals. Therefore, we hypothesized that the global loss of O-GlcNAcylation disrupted genomic and gene-specific 5hmC DNA marks that promoted aberrant gene and protein expression associated with epilepsy. In support of our hypothesis, we found that promoting and restoring global O-GlcNAcylation with Thiamet-G in epileptic rats restored the genomic loss of 5hmC. In addition, treatment with Thiamet-G displayed preferential restoration of 5hmC at promoter and gene body regions of anti-convulsive genes associated with epilepsy. Interestingly, treatment with Thiamet-G had a seizure dampening effect but demonstrated little impact in decreasing/reversing ventricle enlargement. Altogether, our findings have begun to elucidate a novel association between PTM's and epigenetic gene regulation in epilepsy that can demonstrate the therapeutic potential to alleviate the disorder.

Subject Added Entry-Topical Term  

Neurosciences

Subject Added Entry-Topical Term  

Genetics

Subject Added Entry-Topical Term  

Cellular biology

Subject Added Entry-Topical Term  

Physiology

Subject Added Entry-Topical Term  

Medicine

Subject Added Entry-Topical Term  

Histology

Subject Added Entry-Topical Term  

Epidemiology

Subject Added Entry-Topical Term  

Immunology

Subject Added Entry-Topical Term  

Public health

Subject Added Entry-Topical Term  

Pathology

Subject Added Entry-Topical Term  

Health sciences

Subject Added Entry-Topical Term  

Toxicology

Added Entry-Corporate Name  

The University of Alabama at Birmingham Neurobiology

Host Item Entry  

Dissertations Abstracts International. 81-04B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

로그인을 한후 보실 수 있는 자료입니다.

소장사항  

202002 2020

Control Number  

joongbu:566249