Honors Program

University Honors

Date of Award

5-2015

Thesis Professor(s)

Dr. Gregory Ordway

Thesis Professor Department

Pharmacology

Thesis Reader(s)

Dr. Atilla Szebeni, Dr. Michelle Chandley

Abstract

Myocardial infarction (MI), often referred to as a heart attack, is a serious health issue in the United States. There is a well-documented link between MI and major depressive disorder (MDD), with a high incidence of MDD occurring after an MI. Overlapping pathologies have been observed within the hippocampus of the brain in animal models of MI and depression. These observations suggest that pathobiological cross-talk between the heart and brain could have a role in the etiology of MDD that occurs after an MI. Spinal cord stimulation (SCS) has previously been shown to have both cardioprotective and neuroprotective effects post-MI, and hence may protect individuals from developing depression post-MI. In this study, we examined the potential biochemical mechanisms that might underlie the neuroprotective actions of SCS following MI. Brain tissues were obtained from three groups of canines: sham-operated animals, animals subjected to experimental myocardial infarction/mitral regurgitation (MI/MR), and animals subjected to MI/MR that were simultaneously administered SCS. The whole hippocampus and hippocampal dentate gyrus were dissected from frozen brains. Quantitative endpoint-PCR and RT-qPCR techniques were employed to measure select biochemical mediators of neuroprotection, i.e. adenosine A2A receptor, ghrelin, and ghrelin receptor expression in hippocampal samples. SCS induced a significant decrease in A2A receptor expression and a dramatic increase in ghrelin expression in MI/MR canines as compared to the MI/MR group without SCS. These findings suggest that adenosine receptors and ghrelin may play a biochemical role in SCS-induced neuroprotection of the hippocampus. Understanding the neuroprotective actions of SCS has the potential to aid the development of new treatments or preventative measures for depression following a heart attack.

Publisher

East Tennessee State University

Document Type

Honors Thesis - Withheld

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Copyright

Copyright by the authors.

Available for download on Monday, May 07, 2018

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