title: Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a risk factor for age-related dementia and development of neurodegenerative disorders such as Alzheimer's disease that are associated with cognitive decline. The exact mechanism for this risk is unknown but we hypothesized that TBI is exacerbating age-related changes in gene expression. Here, we present evidence in an animal model that experimental TBI increases age-related stochastic gene expression. We compared the variability in expression of several genes associated with cell survival or death, among three groups of laser capture microdissected hippocampal neurons from aging rat brains. TBI increased stochastic fluctuations in gene expression in both dying and surviving neurons compared to the naïve neurons. Increases in random, stochastic fluctuations in prosurvival or prodeath gene expression could potentially alter cell survival or cell death pathways in aging neurons after TBI which may lead to age-related cognitive decline.
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Shearer
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Boone
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Harris
authors.initials: H
authors.lastname: Weisz
authors.affiliation: Office of Biostatistics, University of Texas Medical Branch, 601 Harborside Drive, Galveston, TX, 77555-0830, USA.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Jennings
authors.affiliation: Office of Biostatistics, University of Texas Medical Branch, 601 Harborside Drive, Galveston, TX, 77555-0830, USA.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Parsley
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: DeWitt
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Prough
authors.affiliation: Department of Anesthesiology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0830, USA. hhellmic@utmb.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Hellmich
mesh_terms: D000375:Aging / Q000235:genetics / Q000523:psychology; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000523:psychology; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D006624:Hippocampus / Q000473:pathology*; D061346:Laser Capture Microdissection / Q000379:methods; D009474:Neurons / Q000473:pathology*; D051381:Rats; D013269:Stochastic Processes
keywords: Aging; Hippocampus; Laser capture microdissection; Stochastic gene expression; Traumatic brain injury