Date of Award
Dr. Gregory Ordway
Thesis Professor Department
Dr. Atilla Szebeni, Dr. Michelle Chandley
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.
East Tennessee State University
Honors Thesis - Withheld
Jewett, Benjamin E., "Inverse Changes in Ghrelin and A2A Receptor Gene Expression Levels in the Hippocampus of Heart Failure Canines Following Spinal Cord Stimulation" (2015). Undergraduate Honors Theses. Paper 262. https://dc.etsu.edu/honors/262
Copyright by the authors.
Available for download on Monday, May 07, 2018