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.
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References
Colantonio A, Ratcliff G, Chase S et al (2004) Aging with traumatic brain injury: long-term health conditions. Int J Rehabil Res 27:209–214
Hamm RJ, Jenkins LW, Lyeth BG et al (1991) The effect of age on outcome following traumatic brain injury in rats. J Neurosurg 75:916–921
Lye TC, Shores EA (2000) Traumatic brain injury as a risk factor for Alzheimer’s disease: a review. Neuropsychol Rev 10:115–129
Vincent AS, Roebuck-Spencer TM, Cernich A (2014) Cognitive changes and dementia risk after traumatic brain injury: implications for aging military personnel. Alzheimers Dement 10:S174–S187. doi:10.1016/j.jalz.2014.04.006
Raj A, van Oudenaarden A (2008) Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135:216–226
Martin GM (2012) Stochastic modulations of the pace and patterns of ageing: impacts on quasi-stochastic distributions of multiple geriatric pathologies. Mech Ageing Dev 133:107–111
Wang Q, Huang J, Zhang X et al (2011) The spatial association of gene expression evolves from synchrony to asynchrony and stochasticity with age. PLoS One 6:e24076. doi:10.1371/journal.pone.0024076
Arciniegas D, Adler L, Topkoff J et al (1999) Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation. Brain Inj 13:1–13
Kiraly M, Kiraly SJ (2007) traumatic brain injury and delayed sequelae: a review—traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia. Sci World J 7:1768–1776
Rojo DR, Prough DS, Boone DR et al (2011) Influence of stochastic gene expression on the cell survival rheostat after traumatic brain injury. PLoS One 6:e23111
Schmued LC, Albertson C, Slikker W Jr (1997) Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res 751:37–46
Saunders RL (2002) The impact of aging on head injuries: implications. J Trauma 53:391
Bahar R, Hartmann CH, Rodriguez KA et al (2006) Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441:1011–1014. doi:10.1038/nature04844
Chapman TR, Barrientos RM, Ahrendsen JT et al (2012) Aging and infection reduce expression of specific brain-derived neurotrophic factor mRNAs in hippocampus. Neurobiol Aging 33:832.e1–832.e14. doi:10.1016/j.neurobiolaging.2011.07.015
Schipper HM (2000) Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol 35:821–830
Gardner RC, Burke JF, Nettiksimmons J et al (2014) Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity. JAMA Neurol 71:1490–1497. doi:10.1001/jamaneurol.2014.2668
Acknowledgments
Funding provided by the Department of Anesthesiology and by a Moody Foundation grant to DSD. We thank Christine Courteau-Butler, Andy Hall and Laurie Bolding for editorial support, and Christy Perry for figures and graphs.
Conflict of interest
The authors report no conflict of interest in these studies.
Statement of human and animal rights
The project described in this manuscript did not involve human subjects. The project was conducted under a protocol approved by the Institutional Animal Care and Use Committee. Research animals are housed in a facility that is under supervision of the UTMB Animal Resource Center and their veterinarians. The UTMB Animal Resource Center is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AALAC).
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The authors of this paper have no actual or potential conflicts of interest in relation to the work described in the manuscript. All University of Texas Medical Branch (UTMB) at Galveston personnel participating in research, whether faculty, staff, fellows, or students, are required to make an annual declaration of actual and potential conflicts of interest; the authors of this paper are in compliance with that requirement. Funding was provided by the UTMB Department of Anesthesiology and by a Moody Foundation grant to D. S. DeWitt.
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Shearer, J., Boone, D., Weisz, H. et al. Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury. Aging Clin Exp Res 28, 363–367 (2016). https://doi.org/10.1007/s40520-015-0396-2
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DOI: https://doi.org/10.1007/s40520-015-0396-2