Cecília R. A. Santos

Isabel Gonçalves

José Cipolla-Neto

Markus Krohn

Telma Quintela

Frontiers in Neuroscience

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TYPE EditorialPUBLISHED 27 March 2023DOI 10.3389/fnins.2023.1176084OPEN ACCESSEDITED AND REVIEWED BYLuis de Lecea,Stanford University, United States*CORRESPONDENCETelma Quintelatquintela@fcsaude.ubi.ptSPECIALTY SECTIONThis article was submitted toSleep and Circadian Rhythms,a section of the journalFrontiers in NeuroscienceRECEIVED 28 February 2023ACCEPTED 14 March 2023PUBLISHED 27 March 2023CITATIONSantos CRA, Cipolla-Neto J, Krohn M,Gonçalves I and Quintela T (2023) Editorial:Crossing brain barriers in health and disease:Impact of circadian rhythms.Front. Neurosci. 17:1176084.doi: 10.3389/fnins.2023.1176084COPYRIGHT© 2023 Santos, Cipolla-Neto, Krohn,Gonçalves and Quintela. This is anopen-access article distributed under the termsof the Creative Commons Attribution License(CC BY). The use, distribution or reproductionin other forums is permitted, provided theoriginal author(s) and the copyright owner(s)are credited and that the original publication inthis journal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permitted whichdoes not comply with these terms.Editorial: Crossing brain barriersin health and disease: Impact ofcircadian rhythmsCecília R. A. Santos1, José Cipolla-Neto2, Markus Krohn3,Isabel Gonçalves1 and Telma Quintela1,4*1CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal,2Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo,São Paulo, Brazil, 3Immungenetics AG, Hamburg, Germany, 4UDI-IPG - Unidade de Investigação para oDesenvolvimento do Interior, Instituto Politécnico da Guarda, Guarda, PortugalKEYWORDSbrain barriers, circadian rhythm, brain disease, circadian therapy, suprachiasmatic nucleusEditorial on the Research TopicCrossing brain barriers in health and disease: Impact of circadian rhythmsBrain barriers (BB) are the gatekeepers of the central nervous system, essential toprotect the brain from xenobiotics, microorganisms, and other harmful agents. Conversely,disruption of BB is a key event responsible for several changes during the onset andprogression of brain diseases (Han and Jiang, 2020).Along with BB disruption, disturbances in the circadian rhythms are considered a riskfactor for Alzheimer’s disease andmajor determinants of manymood, anxiety, and psychoticdisorders (Chen et al., 2022).BB functions are regulated by circadian rhythms (Cuddapah et al., 2019; Quintela et al.,2021), act in concert with neuronal and astrocytic activities (Fultz et al., 2019), and thus holdpromise for the improvement of treatments against brain cancer and other brain diseasesby disclosing the most adequate timing of the day to enable the brain uptake of therapeuticdrugs. On the other hand, neurological disorders have their own circadian patterns in termsof symptoms and responsiveness to therapies (Hood and Amir, 2017).If dysfunctions of the BB and disturbed circadian rhythms are clear contributors to braindiseases, it follows that circadian-oriented interventions could prevent or delay the onset ofbrain diseases.Therefore, this Research Topic gathers different contributions highlighting theinvolvement of the circadian rhythms in health and disease, contributing to the earlyidentification and control of brain diseases.It is well-established that disturbances in the circadian rhythms are observed in patientsrecovering from traumatic brain injury (TBI), which are critical for the recuperationprocess. The first article of this Research Topic, shows that circadian rhythms are crucialdeterminants of TBI outcome. The authors showed that health parameters and scores varydepending on the light-dark cycle at which induced TBI occurred, in male Wistar rats(Martinez-Tapiaet al.). Thus, the results of this article will contribute to optimize the medicalprocedure, taking into account the time of the day when TBI occurs.Frontiers inNeuroscience 01 frontiersin.orgSantos et al. 10.3389/fnins.2023.1176084The urgent need for new therapies for primary insomniawith minimal side effects, turned out to be the main objective ofone of the other articles published. Although the transcutaneousauricular vagus nerve stimulation, has been reported as an effectivetreatment for insomnia, the inter-individual variations in theefficacy of this treatment are not well-understood. The authorsobserved that during continuous transcutaneous auricular vagusnerve stimulation, patients with primary insomnia showed variablesensitivity, that might be explained by the distinct control of thesensorimotor network by the autonomic nervous system (Wuet al.).The link between circadian rhythms and mood and anxietydisorders, was another subject addressed in this Research Topic.The authors analyzed the involvement of the master clock, locatedin the suprachiasmatic nucleus (SCN) of the hypothalamus, inregulating psychiatric-related behaviors in mice using optogeneticstimulation paradigms. They concluded that SCN-mediateddampening of rhythms is directly correlated with depressive- andanxiety-like behaviors (Vadnie et al.). Thus, this article establishedan important relationship between the circadian molecular system,namely the SCN, and the psychiatric-related behaviors.Finally, the last published article also tried to relatealterations in biological rhythms with depressive disordersand consequently possible changes in tumor markers, dueto the development of chronic inflammatory diseases. Theyconcluded that the incidence of non-suicidal self-injury, a riskfactor for suicide in depressive patients, was relatively highin adolescents. Furthermore, the construction of an indexincluding a combination of depression score, tumor markerlevels, and age can identify non-suicidal self-injury behaviorsamong adolescent patients with diagnosed depressive disorders (Yiet al.).In summary, this Research Topic is a step forward tounderstanding the influence of circadian rhythms in health anddisease and we hope that the reader will find it a useful referencein the emerging field of adequate “rhythmic” therapeutic strategiestaking into consideration the influence of the circadian biology.Author contributionsTQwrote the first draft. CS, JC-N, MK, and IG provided criticalcomments and editorial suggestions for revisions. All authorsagreed on the submitted version.FundingThis work was developed within the scope of the CICS-UBIprojects UIDB/00709/2020 and UIDP/00709/2020, financed bynational funds through the Portuguese Foundation for Scienceand Technology/MCTES.Conflict of interestMK was employed by Immungenetics AG.The remaining authors declare that the research was conductedin the absence of any commercial or financial relationships thatcould be construed as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.ReferencesChen, S. J., Deng, Y. T., Li, Y. Z., Zhang, Y. R., Zhang, W., Chen, S. D.,et al. (2022). Association of circadian rhythms with brain disorder incidents:a prospective cohort study of 72242 participants. Transl. Psychiatry 12, 514.doi: 10.1038/s41398-022-02278-1Cuddapah, V. A., Zhang, S. L., and Sehgal, A. (2019). Regulation of the blood-brain barrier by circadian rhythms and sleep. Trends Neurosci. (2019) 42, 500–510.doi: 10.1016/j.tins.05, 001.Fultz, N. E., Bonmassar, G., Setsompop, K., Stickgold, R. A., Rosen, B. R., Polimeni,J. R., et al. (2019). Coupled electrophysiological, hemodynamic, and cerebrospinal fluidoscillations in human sleep. Science 366, 628–631. doi: 10.1126/science.aax5440Han, L., and Jiang, C. (2020). Evolution of blood-brain barrier in brain diseases andrelated systemic nanoscale brain-targeting drug delivery strategies. Acta Pharm. Sin. B.(2021) 11, 2306–2325. doi: 10.1016/j.apsb.11, 023Hood, S., and Amir, S. (2017). Neurodegeneration and thecircadian clock. Front. Aging. Neurosci. 9, 170. doi: 10.3389/fnagi.2017.00170Quintela, T., Furtado, A., Duarte, A. C., Goncalves, I., Myung, J., Santos,C. R. A., et al. (2021). The role of circadian rhythm in choroid plexusfunctions. Prog. Neurobiol. 205, 102129. doi: 10.1016/j.pneurobio.2021.102129Frontiers inNeuroscience 02 frontiersin.org

Editorial: Crossing brain barriers in health and disease: Impact of circadian rhythms

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Editorial: Crossing brain barriers in health and disease: Impact of circadian rhythms

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