Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish

Detalhes bibliográficos
Autor(a) principal: Santos, C.
Data de Publicação: 2023
Outros Autores: Valentim, A. M., Félix, L., Balça-Silva, J., Pinto, M. L.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/153625
Resumo: Funding Information: This work was funded by FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through FCT – Portuguese Foundation for Science and Technology under the project FCOMP-01-0124-FEDER-028683 (PTDC/CVT-WEL/4672/2012). Publisher Copyright: © 2023 The Authors
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spelling Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafishCNSDeathKetamineProliferationZebrafishNeuroscience(all)ToxicologySDG 3 - Good Health and Well-beingFunding Information: This work was funded by FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through FCT – Portuguese Foundation for Science and Technology under the project FCOMP-01-0124-FEDER-028683 (PTDC/CVT-WEL/4672/2012). Publisher Copyright: © 2023 The AuthorsZebrafish is known for its widespread neurogenesis and regenerative capacity, as well as several biological advantages, which turned it into a relevant animal model in several areas of research, namely in toxicological studies. Ketamine is a well-known anesthetic used both in human as well as veterinary medicine, due to its safety, short duration and unique mode of action. However, ketamine administration is associated with neurotoxic effects and neuronal death, which renders its use on pediatric medicine problematic. Thus, the evaluation of ketamine effects administration at early stages of neurogenesis is of pivotal importance. The 1‐41–4 somites stage of zebrafish embryo development corresponds to the beginning of segmentation and formation of neural tube. In this species, as well as in other vertebrates, longitudinal studies are scarce, and the evaluation of ketamine long-term effects in adults is poorly understood. This study aimed to assess the effects of ketamine administration at the 1–4 somites stage, both in subanesthetic and anesthetic concentrations, in brain cellular proliferation, pluripotency and death mechanisms in place during early and adult neurogenesis. For that purpose, embryos at the 1–4 somites stage (10.5 h post fertilization - hpf) were distributed into study groups and exposed for 20 min to ketamine concentrations at 0.2/0.8 mg/mL. Animals were grown until defined check points, namely 50 hpf, 144 hpf and 7 months adults. The assessment of the expression and distribution patterns of proliferating cell nuclear antigen (PCNA), of sex-determining region Y-box 2 (Sox 2), apoptosis-inducing factor (AIF) and microtubule-associated protein 1 light chain 3 (LC3) was performed by Western-blot and immunohistochemistry. The results evidenced the main alterations in 144 hpf larvae, namely in autophagy and in cellular proliferation at the highest concentration of ketamine (0.8 mg/mL). Nonetheless, in adults no significant alterations were seen, pointing to a return to a homeostatic stage. This study allowed clarifying some of the aspects pertaining the longitudinal effects of ketamine administration regarding the CNS capacity to proliferate and activate the appropriate cell death and repair mechanisms leading to homeostasis in zebrafish. Moreover, the results indicate that ketamine administration at 1–4 somites stage in the subanesthetic and anesthetic concentrations despite some transitory detrimental effects at 144 hpf, is long-term safe for CNS, which are newly and promising results in this research field.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNSantos, C.Valentim, A. M.Félix, L.Balça-Silva, J.Pinto, M. L.2023-06-05T22:20:54Z2023-072023-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article11application/pdfhttp://hdl.handle.net/10362/153625eng0161-813XPURE: 62438611https://doi.org/10.1016/j.neuro.2023.05.008info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:36:10Zoai:run.unl.pt:10362/153625Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:55:20.993064Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
title Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
spellingShingle Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
Santos, C.
CNS
Death
Ketamine
Proliferation
Zebrafish
Neuroscience(all)
Toxicology
SDG 3 - Good Health and Well-being
title_short Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
title_full Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
title_fullStr Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
title_full_unstemmed Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
title_sort Longitudinal effects of ketamine on cell proliferation and death in the CNS of zebrafish
author Santos, C.
author_facet Santos, C.
Valentim, A. M.
Félix, L.
Balça-Silva, J.
Pinto, M. L.
author_role author
author2 Valentim, A. M.
Félix, L.
Balça-Silva, J.
Pinto, M. L.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Santos, C.
Valentim, A. M.
Félix, L.
Balça-Silva, J.
Pinto, M. L.
dc.subject.por.fl_str_mv CNS
Death
Ketamine
Proliferation
Zebrafish
Neuroscience(all)
Toxicology
SDG 3 - Good Health and Well-being
topic CNS
Death
Ketamine
Proliferation
Zebrafish
Neuroscience(all)
Toxicology
SDG 3 - Good Health and Well-being
description Funding Information: This work was funded by FEDER funds through the Operational Competitiveness Programme – COMPETE and by National Funds through FCT – Portuguese Foundation for Science and Technology under the project FCOMP-01-0124-FEDER-028683 (PTDC/CVT-WEL/4672/2012). Publisher Copyright: © 2023 The Authors
publishDate 2023
dc.date.none.fl_str_mv 2023-06-05T22:20:54Z
2023-07
2023-07-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/153625
url http://hdl.handle.net/10362/153625
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0161-813X
PURE: 62438611
https://doi.org/10.1016/j.neuro.2023.05.008
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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