Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.
Identifieur interne : 000049 ( Main/Corpus ); précédent : 000048; suivant : 000050Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.
Auteurs : Hang Xu ; Xiang Yang Zhang ; Wei Wen Wang ; Jiesi WangSource :
- Frontiers in pharmacology [ 1663-9812 ] ; 2021.
Abstract
Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.
DOI: 10.3389/fphar.2021.633112
PubMed: 33953673
PubMed Central: PMC8089481
Links to Exploration step
pubmed:33953673Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.</title><author><name sortKey="Xu, Hang" sort="Xu, Hang" uniqKey="Xu H" first="Hang" last="Xu">Hang Xu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Xiang Yang" sort="Zhang, Xiang Yang" uniqKey="Zhang X" first="Xiang Yang" last="Zhang">Xiang Yang Zhang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Wei Wen" sort="Wang, Wei Wen" uniqKey="Wang W" first="Wei Wen" last="Wang">Wei Wen Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jiesi" sort="Wang, Jiesi" uniqKey="Wang J" first="Jiesi" last="Wang">Jiesi Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33953673</idno><idno type="pmid">33953673</idno><idno type="doi">10.3389/fphar.2021.633112</idno><idno type="pmc">PMC8089481</idno><idno type="wicri:Area/Main/Corpus">000049</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000049</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.</title><author><name sortKey="Xu, Hang" sort="Xu, Hang" uniqKey="Xu H" first="Hang" last="Xu">Hang Xu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Xiang Yang" sort="Zhang, Xiang Yang" uniqKey="Zhang X" first="Xiang Yang" last="Zhang">Xiang Yang Zhang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Wei Wen" sort="Wang, Wei Wen" uniqKey="Wang W" first="Wei Wen" last="Wang">Wei Wen Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jiesi" sort="Wang, Jiesi" uniqKey="Wang J" first="Jiesi" last="Wang">Jiesi Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Frontiers in pharmacology</title><idno type="ISSN">1663-9812</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33953673</PMID><DateRevised><Year>2021</Year><Month>05</Month><Day>08</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1663-9812</ISSN><JournalIssue CitedMedium="Print"><Volume>12</Volume><PubDate><Year>2021</Year></PubDate></JournalIssue><Title>Frontiers in pharmacology</Title><ISOAbbreviation>Front Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.</ArticleTitle><Pagination><MedlinePgn>633112</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fphar.2021.633112</ELocationID><Abstract><AbstractText>Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.</AbstractText><CopyrightInformation>Copyright © 2021 Xu, Zhang, Wang and Wang.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Hang</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Xiang Yang</ForeName><Initials>XY</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Wei Wen</ForeName><Initials>WW</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Jiesi</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>04</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Pharmacol</MedlineTA><NlmUniqueID>101548923</NlmUniqueID><ISSNLinking>1663-9812</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">AIF1</Keyword><Keyword MajorTopicYN="N">BDNF</Keyword><Keyword MajorTopicYN="N">CRH</Keyword><Keyword MajorTopicYN="N">IL-1β</Keyword><Keyword MajorTopicYN="N">SLC6a4</Keyword><Keyword MajorTopicYN="N">anxiety</Keyword><Keyword MajorTopicYN="N">hydroxychloroquine</Keyword></KeywordList><CoiStatement>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.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>11</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>03</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>5</Month><Day>6</Day><Hour>7</Hour><Minute>2</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>5</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>5</Month><Day>7</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33953673</ArticleId><ArticleId IdType="doi">10.3389/fphar.2021.633112</ArticleId><ArticleId IdType="pii">633112</ArticleId><ArticleId IdType="pmc">PMC8089481</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13208-13</Citation><ArticleIdList><ArticleId IdType="pubmed">16924103</ArticleId></ArticleIdList></Reference><Reference><Citation>CMAJ. 2020 Apr 27;192(17):E450-E453</Citation><ArticleIdList><ArticleId IdType="pubmed">32269021</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet. 2001 Aug 11;358(9280):455-60</Citation><ArticleIdList><ArticleId IdType="pubmed">11513909</ArticleId></ArticleIdList></Reference><Reference><Citation>Drug Saf Case Rep. 2017 Dec;4(1):6</Citation><ArticleIdList><ArticleId IdType="pubmed">28258476</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Med. 1983 Jul 18;75(1A):11-8</Citation><ArticleIdList><ArticleId IdType="pubmed">6408923</ArticleId></ArticleIdList></Reference><Reference><Citation>Ann N Y Acad Sci. 2019 Feb;1437(1):57-67</Citation><ArticleIdList><ArticleId IdType="pubmed">29752710</ArticleId></ArticleIdList></Reference><Reference><Citation>J Basic Clin Pharm. 2016 Mar;7(2):27-31</Citation><ArticleIdList><ArticleId IdType="pubmed">27057123</ArticleId></ArticleIdList></Reference><Reference><Citation>J Clin Psychopharmacol. 1982 Feb;2(1):40-7</Citation><ArticleIdList><ArticleId IdType="pubmed">7040501</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Cell Neurosci. 2013 Mar;53:52-62</Citation><ArticleIdList><ArticleId IdType="pubmed">23064447</ArticleId></ArticleIdList></Reference><Reference><Citation>J Neuroinflammation. 2013 Sep 19;10:116</Citation><ArticleIdList><ArticleId IdType="pubmed">24050835</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2020 Sep;585(7826):584-587</Citation><ArticleIdList><ArticleId IdType="pubmed">32698191</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Pharmacol Ther. 2020 Dec;108(6):1135-1149</Citation><ArticleIdList><ArticleId IdType="pubmed">32687630</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 2020 Nov 19;383(21):2041-2052</Citation><ArticleIdList><ArticleId IdType="pubmed">32706953</ArticleId></ArticleIdList></Reference><Reference><Citation>J Neurol. 2020 Jul;267(7):1880-1882</Citation><ArticleIdList><ArticleId IdType="pubmed">32361836</ArticleId></ArticleIdList></Reference><Reference><Citation>Eur J Clin Invest. 2020 Oct;50(10):e13358</Citation><ArticleIdList><ArticleId IdType="pubmed">32705683</ArticleId></ArticleIdList></Reference><Reference><Citation>FASEB J. 2020 May;34(5):6027-6037</Citation><ArticleIdList><ArticleId IdType="pubmed">32350928</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Case Rep. 2015 Jun;3(6):379-87</Citation><ArticleIdList><ArticleId IdType="pubmed">26185633</ArticleId></ArticleIdList></Reference><Reference><Citation>Science. 2010 Nov 5;330(6005):783-8</Citation><ArticleIdList><ArticleId IdType="pubmed">21051630</ArticleId></ArticleIdList></Reference><Reference><Citation>Compr Psychiatry. 2013 Nov;54(8):1185-9</Citation><ArticleIdList><ArticleId IdType="pubmed">23829886</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Drug Discov. 2012 Feb 01;11(2):141-68</Citation><ArticleIdList><ArticleId IdType="pubmed">22293568</ArticleId></ArticleIdList></Reference><Reference><Citation>Brain Behav Immun. 2019 Jul;79:256-266</Citation><ArticleIdList><ArticleId IdType="pubmed">30772475</ArticleId></ArticleIdList></Reference><Reference><Citation>Neural Plast. 2016;2016:6503162</Citation><ArticleIdList><ArticleId IdType="pubmed">27034848</ArticleId></ArticleIdList></Reference><Reference><Citation>Monaldi Arch Chest Dis. 2020 Mar 30;90(1):</Citation><ArticleIdList><ArticleId IdType="pubmed">32231348</ArticleId></ArticleIdList></Reference><Reference><Citation>Arq Neuropsiquiatr. 2017 Sep;75(9):649-656</Citation><ArticleIdList><ArticleId IdType="pubmed">28977146</ArticleId></ArticleIdList></Reference><Reference><Citation>Prog Mol Biol Transl Sci. 2014;122:169-92</Citation><ArticleIdList><ArticleId IdType="pubmed">24484701</ArticleId></ArticleIdList></Reference><Reference><Citation>Behav Sci (Basel). 2012 Jun 21;2(2):135-71</Citation><ArticleIdList><ArticleId IdType="pubmed">23077729</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2019 Jul;571(7766):456-457</Citation><ArticleIdList><ArticleId IdType="pubmed">31337906</ArticleId></ArticleIdList></Reference><Reference><Citation>Cogn Process. 2012 May;13(2):93-110</Citation><ArticleIdList><ArticleId IdType="pubmed">22160349</ArticleId></ArticleIdList></Reference><Reference><Citation>EMBO Mol Med. 2020 Aug 7;12(8):e12476</Citation><ArticleIdList><ArticleId IdType="pubmed">32715647</ArticleId></ArticleIdList></Reference><Reference><Citation>Handb Exp Pharmacol. 2014;220:223-50</Citation><ArticleIdList><ArticleId IdType="pubmed">24668475</ArticleId></ArticleIdList></Reference><Reference><Citation>Neuropharmacology. 2015 Sep;96(Pt A):11-8</Citation><ArticleIdList><ArticleId IdType="pubmed">25549562</ArticleId></ArticleIdList></Reference><Reference><Citation>Expert Rev Anti Infect Ther. 2021 Jan;19(1):5-16</Citation><ArticleIdList><ArticleId IdType="pubmed">32693652</ArticleId></ArticleIdList></Reference><Reference><Citation>J Neuroimmunol. 2000 Jul 10;107(1):8-20</Citation><ArticleIdList><ArticleId IdType="pubmed">10808046</ArticleId></ArticleIdList></Reference><Reference><Citation>J Natl Med Assoc. 1981 Nov;73(11):1073-6</Citation><ArticleIdList><ArticleId IdType="pubmed">7310924</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000049 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000049 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= CovidChloroV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= pubmed:33953673
|texte= Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i -Sk "pubmed:33953673" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a CovidChloroV1
| This area was generated with Dilib version V0.6.38. |  |