Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among the global youth and commonly results in long-lasting sequelae, including paralysis, epilepsy, and a host of mental disorders such as major depressive disorder. Previous studies were mainly focused on severe TBI as it o...

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Veröffentlicht in:Pharmaceutics 2021-12, Vol.13 (12), p.2169, Article 2169
Hauptverfasser: Yang, Shih-Te, Hung, Hsiu-Yi, Ro, Long-Sun, Liao, Ming-Feng, Amstislavskaya, Tamara G., Tikhonova, Maria A., Yang, Yi-Ling, Lu, Kwok-Tung
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container_end_page
container_issue 12
container_start_page 2169
container_title Pharmaceutics
container_volume 13
creator Yang, Shih-Te
Hung, Hsiu-Yi
Ro, Long-Sun
Liao, Ming-Feng
Amstislavskaya, Tamara G.
Tikhonova, Maria A.
Yang, Yi-Ling
Lu, Kwok-Tung
description Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among the global youth and commonly results in long-lasting sequelae, including paralysis, epilepsy, and a host of mental disorders such as major depressive disorder. Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent f
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Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&amp;E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent for preventing the long-term adverse effect of mTBI-J.</description><identifier>ISSN: 1999-4923</identifier><identifier>EISSN: 1999-4923</identifier><identifier>DOI: 10.3390/pharmaceutics13122169</identifier><identifier>PMID: 34959450</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Alzheimer's disease ; Antidepressants ; Brain damage ; Brain research ; Brain-derived neurotrophic factor ; Contusions ; depression-like behavior ; dorsal hippocampus ; Edema ; Intracranial pressure ; juvenile ; Kinases ; Laboratory animals ; Life Sciences &amp; Biomedicine ; Mental depression ; mild traumatic brain injury ; Mortality ; Pharmacology &amp; Pharmacy ; Post traumatic stress disorder ; Preferences ; Science &amp; Technology ; Sucrose ; Traumatic brain injury ; ventral hippocampus</subject><ispartof>Pharmaceutics, 2021-12, Vol.13 (12), p.2169, Article 2169</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>true</woscitedreferencessubscribed><woscitedreferencescount>5</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000736517800001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c505t-ff3b380b8a0a2e47c674a31863ef194750add0132b8c1d7ba603e446d44e2b463</citedby><cites>FETCH-LOGICAL-c505t-ff3b380b8a0a2e47c674a31863ef194750add0132b8c1d7ba603e446d44e2b463</cites><orcidid>0000-0001-7908-4267 ; 0000-0002-4265-8981 ; 0000-0002-6996-8277</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/PMC8704538/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704538/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,39263,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34959450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Shih-Te</creatorcontrib><creatorcontrib>Hung, Hsiu-Yi</creatorcontrib><creatorcontrib>Ro, Long-Sun</creatorcontrib><creatorcontrib>Liao, Ming-Feng</creatorcontrib><creatorcontrib>Amstislavskaya, Tamara G.</creatorcontrib><creatorcontrib>Tikhonova, Maria A.</creatorcontrib><creatorcontrib>Yang, Yi-Ling</creatorcontrib><creatorcontrib>Lu, Kwok-Tung</creatorcontrib><title>Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age</title><title>Pharmaceutics</title><addtitle>PHARMACEUTICS</addtitle><addtitle>Pharmaceutics</addtitle><description>Traumatic brain injury (TBI) is a leading cause of mortality and morbidity among the global youth and commonly results in long-lasting sequelae, including paralysis, epilepsy, and a host of mental disorders such as major depressive disorder. Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&amp;E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent for preventing the long-term adverse effect of mTBI-J.</description><subject>Alzheimer's disease</subject><subject>Antidepressants</subject><subject>Brain damage</subject><subject>Brain research</subject><subject>Brain-derived neurotrophic factor</subject><subject>Contusions</subject><subject>depression-like behavior</subject><subject>dorsal hippocampus</subject><subject>Edema</subject><subject>Intracranial pressure</subject><subject>juvenile</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Mental depression</subject><subject>mild traumatic brain injury</subject><subject>Mortality</subject><subject>Pharmacology &amp; Pharmacy</subject><subject>Post traumatic stress disorder</subject><subject>Preferences</subject><subject>Science &amp; Technology</subject><subject>Sucrose</subject><subject>Traumatic brain injury</subject><subject>ventral hippocampus</subject><issn>1999-4923</issn><issn>1999-4923</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNktFu0zAUhiMEYtPYI4AscYMEATt2EvsGqesYKypCQuU6cpzjxiWxi-0U7SV4Ztx1VBviAt_YPv7O7-PjP8ueE_yWUoHfbXvpR6lgikYFQklRkEo8yk6JECJnoqCP761PsvMQNjgNSgmn4ml2QpkoBSvxafZr3ntnjUKzbjTWhOhlNM4ip1H9hueX11doCSGADSj2gC5h69M2EflgvgO6gF7ujPN7_tO0A2sGQJ_N0KGVl9OYtBS68NJYtLCbyd-kMMgIHfoqY0AyolUPxqfLpyGi2RqeZU-0HAKc381n2berD6v5db788nExny1zVeIy5lrTlnLccollAaxWVc1kelxFQRPB6hLLrsOEFi1XpKtbWWEKjFUdY1C0rKJn2eKg2zm5abbejNLfNE6a5jbg_LqRPhU_QFNT1QqVmonblinCuBZKa051ISrNKEta7w9a26kdoVNgUxOHB6IPT6zpm7XbNbzGrKQ8Cby6E_DuxwQhNqMJCoZBWnBTaIqKlITUotrX_fIvdOMmb1Or9lTBi_TJdaLKA6W8C8GDPhZDcLM3UPNPA6W8F_dfcsz6Y5cE8APwE1qngzJgFRyx5LCaViWp-d5sZG7irZfmbrIxpb7-_1T6G-Sd5kE</recordid><startdate>20211216</startdate><enddate>20211216</enddate><creator>Yang, Shih-Te</creator><creator>Hung, Hsiu-Yi</creator><creator>Ro, Long-Sun</creator><creator>Liao, Ming-Feng</creator><creator>Amstislavskaya, Tamara G.</creator><creator>Tikhonova, Maria A.</creator><creator>Yang, Yi-Ling</creator><creator>Lu, Kwok-Tung</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7908-4267</orcidid><orcidid>https://orcid.org/0000-0002-4265-8981</orcidid><orcidid>https://orcid.org/0000-0002-6996-8277</orcidid></search><sort><creationdate>20211216</creationdate><title>Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age</title><author>Yang, Shih-Te ; 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Previous studies were mainly focused on severe TBI as it occurs in adults. This study explored the long-term adverse effect of mild TBI in juvenile animals (mTBI-J). Male Sprague Dawley rats received mTBI-J or sham treatment at six weeks old, then underwent behavioral, biochemical, and histological experiments three weeks later (at nine weeks old). TTC staining, H&amp;E staining, and brain edema measurement were applied to evaluate the mTBI-J induced cerebral damage. The forced swimming test (FST) and sucrose preference test (SPT) were applied for measuring depression-like behavior. The locomotor activity test (LAT) was performed to examine mTBI-J treatment effects on motor function. After the behavioral experiments, the dorsal hippocampus (dHip) and ventral hippocampus (vHip) were dissected out for western blotting to examine the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). Finally, a TrkB agonist 7,8-DHF was injected intraperitoneally to evaluate its therapeutic effect on the mTBI-J induced behavioral abnormalities at the early adult age. Results showed that a mild brain edema occurred, but no significant neural damage was found in the mTBI-J treated animals. In addition, a significant increase of depression-like behaviors was observed in the mTBI-J treated animals; the FST revealed an increase in immobility, and a decrease in sucrose consumption was found in the mTBI-J treated animals. There were no differences observed in the total distance traveled of the LAT and the fall latency of the rotarod test. The hippocampal BDNF expression, but not the TrkB, were significantly reduced in mTBI-J, and the mTBI-J treatment-induced depression-like behavior was lessened after four weeks of 7,8-DHF administration. Collectively, these results indicate that even a mild juvenile TBI treatment that did not produce motor deficits or significant histological damage could have a long-term adverse effect that could be sustained to adulthood, which raises the depression-like behavior in the adult age. In addition, chronic administration of 7,8-DHF lessens the mTBI-J treatment-induced depression-like behaviors in adult rats. We suggest the potential usage of 7,8-DHF as a therapeutic agent for preventing the long-term adverse effect of mTBI-J.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34959450</pmid><doi>10.3390/pharmaceutics13122169</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-7908-4267</orcidid><orcidid>https://orcid.org/0000-0002-4265-8981</orcidid><orcidid>https://orcid.org/0000-0002-6996-8277</orcidid><oa>free_for_read</oa></addata></record>
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subjects Alzheimer's disease
Antidepressants
Brain damage
Brain research
Brain-derived neurotrophic factor
Contusions
depression-like behavior
dorsal hippocampus
Edema
Intracranial pressure
juvenile
Kinases
Laboratory animals
Life Sciences & Biomedicine
Mental depression
mild traumatic brain injury
Mortality
Pharmacology & Pharmacy
Post traumatic stress disorder
Preferences
Science & Technology
Sucrose
Traumatic brain injury
ventral hippocampus
title Chronic Administration of 7,8-DHF Lessens the Depression-like Behavior of Juvenile Mild Traumatic Brain Injury Treated Rats at Their Adult Age
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