Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress
Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determi...
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| Veröffentlicht in: | International journal of molecular sciences 2021-09, Vol.22 (18), p.9960 |
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| creator | Sung, Minkyoung Sung, Soo-Eun Kang, Kyung-Ku Choi, Joo-Hee Lee, Sijoon Kim, KilSoo Lim, Ju-Hyeon Lee, Gun Woo Rim, Hyo-Deog Kim, Byung-Soo Won, Seunghee Kim, Kyungmin Jang, Seoyoung Seo, Min-Soo Woo, Jungmin |
| description | Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers. |
| doi_str_mv | 10.3390/ijms22189960 |
| format | Article |
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Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22189960</identifier><identifier>PMID: 34576126</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute Disease ; Alzheimer's disease ; Animal models ; Animals ; Biomarkers ; Biomarkers - blood ; Brain damage ; Brain injury ; Brain-derived neurotrophic factor ; Cancer ; Cardiovascular disease ; Exosomes ; Exosomes - metabolism ; Exosomes - ultrastructure ; Feet ; Footshock ; Gene Ontology ; Homeostasis ; Hormones ; Hormones - metabolism ; Hypothalamo-Hypophyseal System - metabolism ; Inflammation ; Inflammation - blood ; Inflammation - genetics ; Inflammation - pathology ; Inflammatory bowel disease ; Male ; MicroRNAs ; MicroRNAs - blood ; MicroRNAs - genetics ; miRNA ; Neurons - metabolism ; Next-generation sequencing ; Parkinson's disease ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological - blood ; Stress, Psychological - genetics</subject><ispartof>International journal of molecular sciences, 2021-09, Vol.22 (18), p.9960</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-81fcf78f53572139b3976fab75a36a8bdb3897c584c85e1ec0d9759b8f45079b3</citedby><cites>FETCH-LOGICAL-c412t-81fcf78f53572139b3976fab75a36a8bdb3897c584c85e1ec0d9759b8f45079b3</cites><orcidid>0000-0001-9971-2443 ; 0000-0001-7370-2685 ; 0000-0001-7817-2222 ; 0000-0002-8441-0802 ; 0000-0001-9304-0404</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470330/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470330/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34576126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sung, Minkyoung</creatorcontrib><creatorcontrib>Sung, Soo-Eun</creatorcontrib><creatorcontrib>Kang, Kyung-Ku</creatorcontrib><creatorcontrib>Choi, Joo-Hee</creatorcontrib><creatorcontrib>Lee, Sijoon</creatorcontrib><creatorcontrib>Kim, KilSoo</creatorcontrib><creatorcontrib>Lim, Ju-Hyeon</creatorcontrib><creatorcontrib>Lee, Gun Woo</creatorcontrib><creatorcontrib>Rim, Hyo-Deog</creatorcontrib><creatorcontrib>Kim, Byung-Soo</creatorcontrib><creatorcontrib>Won, Seunghee</creatorcontrib><creatorcontrib>Kim, Kyungmin</creatorcontrib><creatorcontrib>Jang, Seoyoung</creatorcontrib><creatorcontrib>Seo, Min-Soo</creatorcontrib><creatorcontrib>Woo, Jungmin</creatorcontrib><title>Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.</description><subject>Acute Disease</subject><subject>Alzheimer's disease</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Brain damage</subject><subject>Brain injury</subject><subject>Brain-derived neurotrophic factor</subject><subject>Cancer</subject><subject>Cardiovascular disease</subject><subject>Exosomes</subject><subject>Exosomes - metabolism</subject><subject>Exosomes - ultrastructure</subject><subject>Feet</subject><subject>Footshock</subject><subject>Gene Ontology</subject><subject>Homeostasis</subject><subject>Hormones</subject><subject>Hormones - metabolism</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Inflammation - genetics</subject><subject>Inflammation - pathology</subject><subject>Inflammatory bowel disease</subject><subject>Male</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Neurons - metabolism</subject><subject>Next-generation sequencing</subject><subject>Parkinson's disease</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stress, Psychological - blood</subject><subject>Stress, Psychological - genetics</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVkMtLAzEQxoMotj5unmXBq6t5bpKLUGt9YKlg9RyyaaJbu01Ndov-90ZaSz3NMPPjm28-AE4QvCBEwstqWkeMkZCygDugiyjGOYQF393qO-AgximEmGAm90GHUMYLhIsueBzb0Nb5jQ3V0k6ykW2Dn-tZNvjy0depqavnUS9mOmbXVRqEDxti5l3WM21js7Fd2pBKE2yMR2DP6Vm0x-t6CF5vBy_9-3z4dPfQ7w1zQxFucoGccVw4RhjHiMiSSF44XXKmSaFFOSmJkNwwQY1gFlkDJ5IzWQpHGeQJPwRXK91FW9Z2Yuy8CXqmFqFK_r6V15X6v5lX7-rNL5WgHBICk8DZWiD4z9bGRk19G9LbUeEUDCWUsyJR5yvKBB9jsG5zAUH1G73ajj7hp9uuNvBf1uQHIid_jw</recordid><startdate>20210915</startdate><enddate>20210915</enddate><creator>Sung, Minkyoung</creator><creator>Sung, Soo-Eun</creator><creator>Kang, Kyung-Ku</creator><creator>Choi, Joo-Hee</creator><creator>Lee, Sijoon</creator><creator>Kim, KilSoo</creator><creator>Lim, Ju-Hyeon</creator><creator>Lee, Gun Woo</creator><creator>Rim, Hyo-Deog</creator><creator>Kim, Byung-Soo</creator><creator>Won, Seunghee</creator><creator>Kim, Kyungmin</creator><creator>Jang, Seoyoung</creator><creator>Seo, Min-Soo</creator><creator>Woo, Jungmin</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9971-2443</orcidid><orcidid>https://orcid.org/0000-0001-7370-2685</orcidid><orcidid>https://orcid.org/0000-0001-7817-2222</orcidid><orcidid>https://orcid.org/0000-0002-8441-0802</orcidid><orcidid>https://orcid.org/0000-0001-9304-0404</orcidid></search><sort><creationdate>20210915</creationdate><title>Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress</title><author>Sung, Minkyoung ; Sung, Soo-Eun ; Kang, Kyung-Ku ; Choi, Joo-Hee ; Lee, Sijoon ; Kim, KilSoo ; Lim, Ju-Hyeon ; Lee, Gun Woo ; Rim, Hyo-Deog ; Kim, Byung-Soo ; Won, Seunghee ; Kim, Kyungmin ; Jang, Seoyoung ; Seo, Min-Soo ; Woo, Jungmin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-81fcf78f53572139b3976fab75a36a8bdb3897c584c85e1ec0d9759b8f45079b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute Disease</topic><topic>Alzheimer's disease</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biomarkers - 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Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. 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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acute Disease Alzheimer's disease Animal models Animals Biomarkers Biomarkers - blood Brain damage Brain injury Brain-derived neurotrophic factor Cancer Cardiovascular disease Exosomes Exosomes - metabolism Exosomes - ultrastructure Feet Footshock Gene Ontology Homeostasis Hormones Hormones - metabolism Hypothalamo-Hypophyseal System - metabolism Inflammation Inflammation - blood Inflammation - genetics Inflammation - pathology Inflammatory bowel disease Male MicroRNAs MicroRNAs - blood MicroRNAs - genetics miRNA Neurons - metabolism Next-generation sequencing Parkinson's disease Rats Rats, Sprague-Dawley Stress, Psychological - blood Stress, Psychological - genetics |
| title | Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress |
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