Physical Medicine & Rehabilitation

Biography

Biography: David T Denhardt

Abstract

“Stress” can be broadly defined as any event that challenges homeostasis to such an extent that the body and brain cannot respond adequately, thus resulting in maladjusted physiology and behavior. Much of the response is mediated via the HPA(hypothalamus-pituitary-adrenal) axis and results in the production of glucocorticoids and other effector hormones. DNA is compacted into chromatin, the genetic constituent of chromosomes, by complexing with a small family of proteins called histones. A dozen or so enzymes have been characterized recently that can modify nucleotides in the DNA (methylation of certain cytosines, often in CpG islands) and amino acids in histones, usually strategically located lysines near promoter regions, which can be modified by the addition of methyl or acetyl groups. These and other modifications, called marks, have the epigenetic (on top of the genetics) consequence of increasing or decreasing the amount of the protein made by that gene. Several types of RNA molecules can also epigenetically regulate gene expression.These epigenetic regulators will be briefl y reviewed. Severe or repeated concussions sustained in contact sports can result in chronic traumatic encephalopathy (CTE), causing prolonged or permanent changes in personality and possibly leading to an early death. Selected research by O Almeida, W Brown, S Horsburgh, and E Lagarde will be briefly discussed to illuminate the epigenetic mechanisms that could contribute to concussion-induced impairments in the quality of life. What is known about the relation between post-concussion syndrome and post traumatic stress disorder following traumatic brain injury will be summarized.