Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans
More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study s...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1473 |
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| author | Rekha S. Patel Meredith Krause-Hauch Kimbra Kenney Shannon Miles Risa Nakase-Richardson Niketa A. Patel |
| author_facet | Rekha S. Patel Meredith Krause-Hauch Kimbra Kenney Shannon Miles Risa Nakase-Richardson Niketa A. Patel |
| author_sort | Rekha S. Patel |
| collection | DOAJ |
| description | More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated with rmTBI years after the incidences. Serum samples were obtained from Long-Term Impact of Military-Relevant Brain-Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC CENC) repository, from participants unexposed to TBI or who had rmTBI. Four lncRNAs were identified as consistently present in all samples, as detected via droplet digital PCR and packaged in exosomes enriched for CNS origin. The results, using qPCR, demonstrated that the lncRNA VLDLR-AS1 levels were significantly lower among individuals with rmTBI compared to those with no lifetime TBI. ROC analysis determined an AUC of 0.74 (95% CI: 0.6124 to 0.8741; <i>p</i> = 0.0012). The optimal cutoff for VLDLR-AS1 was ≤153.8 ng. A secondary analysis of clinical data from LIMBIC CENC was conducted to evaluate the psychological symptom burden, and the results show that lncRNAs VLDLR-AS1 and MALAT1 are correlated with symptoms of depression. In conclusion, lncRNA VLDLR-AS1 may serve as a blood biomarker for identifying chronic rmTBI and depression in patients. |
| first_indexed | 2024-03-08T03:55:49Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:49Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9c6d04b1a9834cc5ba3eed7ce4a8a7072024-02-09T15:13:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01253147310.3390/ijms25031473Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US VeteransRekha S. Patel0Meredith Krause-Hauch1Kimbra Kenney2Shannon Miles3Risa Nakase-Richardson4Niketa A. Patel5Research Service, James A. Haley Veteran’s Hospital, 13000 Bruce B Downs Blvd., Tampa, FL 33612, USADepartment of Molecular Medicine, University of South Florida, Tampa, FL 33612, USADepartment of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USAResearch Service, James A. Haley Veteran’s Hospital, 13000 Bruce B Downs Blvd., Tampa, FL 33612, USAChief of Staff Office, James A. Haley Veteran’s Hospital, Tampa, FL 33612, USAResearch Service, James A. Haley Veteran’s Hospital, 13000 Bruce B Downs Blvd., Tampa, FL 33612, USAMore than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated with rmTBI years after the incidences. Serum samples were obtained from Long-Term Impact of Military-Relevant Brain-Injury Consortium Chronic Effects of Neurotrauma Consortium (LIMBIC CENC) repository, from participants unexposed to TBI or who had rmTBI. Four lncRNAs were identified as consistently present in all samples, as detected via droplet digital PCR and packaged in exosomes enriched for CNS origin. The results, using qPCR, demonstrated that the lncRNA VLDLR-AS1 levels were significantly lower among individuals with rmTBI compared to those with no lifetime TBI. ROC analysis determined an AUC of 0.74 (95% CI: 0.6124 to 0.8741; <i>p</i> = 0.0012). The optimal cutoff for VLDLR-AS1 was ≤153.8 ng. A secondary analysis of clinical data from LIMBIC CENC was conducted to evaluate the psychological symptom burden, and the results show that lncRNAs VLDLR-AS1 and MALAT1 are correlated with symptoms of depression. In conclusion, lncRNA VLDLR-AS1 may serve as a blood biomarker for identifying chronic rmTBI and depression in patients.https://www.mdpi.com/1422-0067/25/3/1473mild traumatic brain injurylncRNAlincRNAexosomesVLDLR-AS1MALAT1 |
| spellingShingle | Rekha S. Patel Meredith Krause-Hauch Kimbra Kenney Shannon Miles Risa Nakase-Richardson Niketa A. Patel Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans International Journal of Molecular Sciences mild traumatic brain injury lncRNA lincRNA exosomes VLDLR-AS1 MALAT1 |
| title | Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans |
| title_full | Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans |
| title_fullStr | Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans |
| title_full_unstemmed | Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans |
| title_short | Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans |
| title_sort | long noncoding rna vldlr as1 levels in serum correlate with combat related chronic mild traumatic brain injury and depression symptoms in us veterans |
| topic | mild traumatic brain injury lncRNA lincRNA exosomes VLDLR-AS1 MALAT1 |
| url | https://www.mdpi.com/1422-0067/25/3/1473 |
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