Cerebrospinal Fluid MicroRNA Changes in Cognitively Normal Veterans With a History of Deployment-Associated Mild Traumatic Brain Injury.

Autor:	Lusardi TA; Knight Cancer Institute, Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, United States., Sandau US; Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States., Sakhanenko NA; Pacific Northwest Research Institute, Seattle, WA, United States., Baker SCB; Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States., Wiedrick JT; Biostatistics & Design Program, Oregon Health & Science University, Portland, OR, United States., Lapidus JA; Biostatistics & Design Program, Oregon Health & Science University, Portland, OR, United States., Raskind MA; Northwest Mental Illness, Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States., Li G; Northwest Mental Illness, Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States.; Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States., Peskind ER; Northwest Mental Illness, Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, United States.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States., Galas DJ; Pacific Northwest Research Institute, Seattle, WA, United States., Quinn JF; Department of Neurology, Oregon Health & Science University, Portland, OR, United States.; Parkinson Center and Movement Disorders Program, School of Medicine, Oregon Health & Science University, Portland, OR, United States.; Portland VAMC Parkinson's Disease Research, Education, and Clinical Center, Portland, OR, United States., Saugstad JA; Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2021 Sep 09; Vol. 15, pp. 720778. Date of Electronic Publication: 2021 Sep 09 (Print Publication: 2021).
DOI:	10.3389/fnins.2021.720778
Abstrakt:	A history of traumatic brain injury (TBI) increases the odds of developing Alzheimer's disease (AD). The long latent period between injury and dementia makes it difficult to study molecular changes initiated by TBI that may increase the risk of developing AD. MicroRNA (miRNA) levels are altered in TBI at acute times post-injury (<4 weeks), and in AD. We hypothesized that miRNA levels in cerebrospinal fluid (CSF) following TBI in veterans may be indicative of increased risk for developing AD. Our population of interest is cognitively normal veterans with a history of one or more mild TBI (mTBI) at a chronic time following TBI. We measured miRNA levels in CSF from three groups of participants: (1) community controls with no lifetime history of TBI (ComC); (2) deployed Iraq/Afghanistan veterans with no lifetime history of TBI (DepC), and (3) deployed Iraq/Afghanistan veterans with a history of repetitive blast mTBI (DepTBI). CSF samples were collected at the baseline visit in a longitudinal, multimodal assessment of Gulf War veterans, and represent a heterogenous group of male veterans and community controls. The average time since the last blast mTBI experienced was 4.7 ± 2.2 years [1.5 - 11.5]. Statistical analysis of TaqMan TM miRNA array data revealed 18 miRNAs with significant differential expression in the group comparisons: 10 between DepTBI and ComC, 7 between DepC and ComC, and 8 between DepTBI and DepC. We also identified 8 miRNAs with significant differential detection in the group comparisons: 5 in DepTBI vs. ComC, 3 in DepC vs. ComC, and 2 in DepTBI vs. DepC. When we applied our previously developed multivariable dependence analysis, we found 13 miRNAs (6 of which are altered in levels or detection) that show dependencies with participant phenotypes, e.g., ApoE. Target prediction and pathway analysis with miRNAs differentially expressed in DepTBI vs. either DepC or ComC identified canonical pathways highly relevant to TBI including senescence and ephrin receptor signaling, respectively. This study shows that both TBI and deployment result in persistent changes in CSF miRNA levels that are relevant to known miRNA-mediated AD pathology, and which may reflect early events in AD. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Lusardi, Sandau, Sakhanenko, Baker, Wiedrick, Lapidus, Raskind, Li, Peskind, Galas, Quinn and Saugstad.)
Databáze:	MEDLINE
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