Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain
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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.
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Excerpt
Hydroxychloroquine induces anxiety-like, but not depression-like behavior in mice
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SciScore for 10.1101/2020.09.27.316158: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All procedures were approved by the Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences and performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Randomization After a week of adaptation, the mice were randomly divided into two groups: the immediate group and the lasting group. Blinding The exploration of each mice was recorded with an overhead camera and then hand-scored by a pretrained independent investigator blinded to the experimental groups. Power Analysis not detected. Sex as a biological variable Animals: The male C57BL/6J mice used in this study were purchased … SciScore for 10.1101/2020.09.27.316158: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All procedures were approved by the Institutional Review Board of the Institute of Psychology, Chinese Academy of Sciences and performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Randomization After a week of adaptation, the mice were randomly divided into two groups: the immediate group and the lasting group. Blinding The exploration of each mice was recorded with an overhead camera and then hand-scored by a pretrained independent investigator blinded to the experimental groups. Power Analysis not detected. Sex as a biological variable Animals: The male C57BL/6J mice used in this study were purchased from Vital River Laboratory Animal Center (Beijing, China) at the age of 8 weeks. Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources Animals: The male C57BL/6J mice used in this study were purchased from Vital River Laboratory Animal Center (Beijing, China) at the age of 8 weeks. C57BL/6Jsuggested: RRID:IMSR_JAX:000664)Software and Algorithms Sentences Resources The following forward (F) and reverse (R) primers (BGI Tech, Beijing, China) were used: Statistical Analysis: The data are presented as the mean ± SEM and were analyzed by GraphPad 8.0. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 8 and 9. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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