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Oxidative DNA Damage in Brainstem Oligodendrocytes in Depressed Suicide Victims

2014 Standard Research Grant
Amount Awarded: $89,972
Focus Area: Genetic Studies

Gregory Ordway, Ph.D.
East Tennessee State University, Quillen College of Medicine

Inside the Research

Bio: Dr. Ordway received his Ph.D. in pharmacology from Ohio State University in 1985.  He is currently a Professor in the Department of Biomedical Sciences at Quillen College of Medicine at East Tennessee State University.

Grant Categories: Neurobiological studies, brain functioning studies

Abstract: The body responds to stress in many ways that affect genetic material, inflammatory response and stress-related hormones. Exposure to stress is a major contributor to the development of psychiatric disorders like major depressive disorder (MDD) and factors related to suicide risk.  DNA (deoxyribonucleic acid) is the genetic material found in every cell that directs the development of proteins and at the end of DNA, like a cap, there is a telomere that gets worn away with aging. Recent studies suggest that stress speeds up cellular aging and this process can be assessed by measuring telomeric DNA length in the blood cells from chronically stressed humans. Recently it has been demonstrated that depression and suicide are associated with advanced aging/oxidative DNA damage that occurs in a specific type of brain cell (oligodendrocyte) that provides insulation to electrical conduction along neurons in the brain.  This study will investigate the potential for advanced cellular aging to affect these cells in an area of the brain previously associated with depression and suicide. The study will examine relative telomere lengths; oxidative DNA damage; and gene expression. Tissue samples for twelve pairs of subjects/controls from three brain banks will be analyzed. Subjects will be individuals with MDD who died by suicide and a healthy comparison group who died by accidents or natural causes. Diagnoses will be determined through post-mortem interviews at time of death. Greater understanding of the molecular pathology of oligodendrocytes may yield clues to the causes of depression and suicide.

Impact: Identification of unique molecular targets for therapies that are specifically designed to lessen stress-induced acceleration of cellular aging and the associated negative consequences.