Publicação
hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation
| Resumo: | Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1. SC is an easily available and popular alternative to cannabis, and their molecular structure is always changing, increasing the hazard for the general population. The popularity of cannabis and its derivatives may lead, and often does, to a child's exposure to cannabis both in utero and through breastfeeding by a drug-consuming mother. Prenatal exposure to cannabis has been associated with an altered rate of mental development and significant changes in nervous system functioning. However, the understanding of mechanisms of its action on developing the human CNS is still lacking. We investigated the effect of continuous exposure to cannabinoids on developing human neurons, mimicking the prenatal exposure by drug-consuming mother. Two human induced pluripotent stem cells (hiPSC) lines were induced to differentiate into neuronal cells and exposed for 37 days to cannabidiol (CBD), Δ9-THC, and two SCs, THJ-018 and EG-018. Both Δ9-THC and SC, at 10 μM, promote precocious neuronal and glial differentiation, while CBD at the same concentration is neurotoxic. Neurons exposed to Δ9-THC and SC show abnormal functioning of voltage-gated calcium channels when stimulated by extracellular potassium. In sum, all studied substances have a profound impact on the developing neurons, highlighting the importance of thorough research on the impact of prenatal exposure to natural and SC. |
|---|---|
| Autores principais: | Miranda, Cláudia C. |
| Outros Autores: | Barata, Tiago; Vaz, Sandra H.; Ferreira, Carla; Quintas, Alexandre; Bekman, Evguenia |
| Assunto: | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809416373764096 |
|---|---|
| author | Miranda, Cláudia C. |
| author2 | Barata, Tiago Vaz, Sandra H. Ferreira, Carla Quintas, Alexandre Bekman, Evguenia |
| author2_role | author author author author author |
| author_facet | Miranda, Cláudia C. Barata, Tiago Vaz, Sandra H. Ferreira, Carla Quintas, Alexandre Bekman, Evguenia |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Miranda, Cláudia C.\",\"Person.identifier.orcid\":\"0000-0001-8602-6014\"},{\"Person.name\":\"Barata, Tiago\",\"Person.identifier.orcid\":\"0000-0002-1483-7990\"},{\"Person.name\":\"Vaz, Sandra H.\",\"Person.identifier.orcid\":\"0000-0003-4258-9397\"},{\"Person.name\":\"Ferreira, Carla\"},{\"Person.name\":\"Quintas, Alexandre\",\"Person.identifier.orcid\":\"0000-0002-5188-0453\"},{\"Person.name\":\"Bekman, Evguenia\",\"Person.identifier.orcid\":\"0000-0002-3963-1358\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Miranda, Cláudia C. Barata, Tiago Vaz, Sandra H. Ferreira, Carla Quintas, Alexandre Bekman, Evguenia |
| datacite.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-06-06T14:41:39Z |
| datacite.date.embargoed.fl_str_mv | 2022-06-06T14:41:39Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| datacite.titles.title.fl_str_mv | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Miranda, Cláudia C. Barata, Tiago Vaz, Sandra H. Ferreira, Carla Quintas, Alexandre Bekman, Evguenia |
| dc.date.Accepted.fl_str_mv | 2020-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-06-06T14:41:39Z |
| dc.date.embargoed.fl_str_mv | 2022-06-06T14:41:39Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/53284 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Frontiers |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| dc.title.fl_str_mv | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1. SC is an easily available and popular alternative to cannabis, and their molecular structure is always changing, increasing the hazard for the general population. The popularity of cannabis and its derivatives may lead, and often does, to a child's exposure to cannabis both in utero and through breastfeeding by a drug-consuming mother. Prenatal exposure to cannabis has been associated with an altered rate of mental development and significant changes in nervous system functioning. However, the understanding of mechanisms of its action on developing the human CNS is still lacking. We investigated the effect of continuous exposure to cannabinoids on developing human neurons, mimicking the prenatal exposure by drug-consuming mother. Two human induced pluripotent stem cells (hiPSC) lines were induced to differentiate into neuronal cells and exposed for 37 days to cannabidiol (CBD), Δ9-THC, and two SCs, THJ-018 and EG-018. Both Δ9-THC and SC, at 10 μM, promote precocious neuronal and glial differentiation, while CBD at the same concentration is neurotoxic. Neurons exposed to Δ9-THC and SC show abnormal functioning of voltage-gated calcium channels when stimulated by extracellular potassium. In sum, all studied substances have a profound impact on the developing neurons, highlighting the importance of thorough research on the impact of prenatal exposure to natural and SC. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/e0b4249e-f4ae-4cef-a3a7-8b12a5fd7df6/download |
| funding.funder.alternateName_str_mv | FCT FCT EC |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100008530 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia European Commission |
| funding.name_str_mv | 6817 - DCRRNI ID H2020 |
| id | ul_c8ebc239d6928ca1cc2879d3c79abc02 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/53284 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/53284 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Miranda, Cláudia C. Miranda, Cláudia C. https://www.ciencia-id.pt/C519-E3D0-A3BF C519-E3D0-A3BF http://orcid.org/0000-0001-8602-6014 0000-0001-8602-6014 Barata, Tiago Barata, Tiago http://orcid.org/0000-0002-1483-7990 0000-0002-1483-7990 Vaz, Sandra H. Vaz, Sandra H. https://www.ciencia-id.pt/0E1C-952D-61BE 0E1C-952D-61BE http://orcid.org/0000-0003-4258-9397 0000-0003-4258-9397 Ferreira, Carla Quintas, Alexandre Quintas, Alexandre https://www.ciencia-id.pt/EF1A-A226-AC0F EF1A-A226-AC0F http://orcid.org/0000-0002-5188-0453 0000-0002-5188-0453 Bekman, Evguenia Bekman, Evguenia https://www.ciencia-id.pt/6D1D-1265-F8B6 6D1D-1265-F8B6 http://orcid.org/0000-0002-3963-1358 0000-0002-3963-1358 |
| publishDate | 2020 |
| publisher.none.fl_str_mv | Frontiers |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engFrontierspt_PTPhytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1. SC is an easily available and popular alternative to cannabis, and their molecular structure is always changing, increasing the hazard for the general population. The popularity of cannabis and its derivatives may lead, and often does, to a child's exposure to cannabis both in utero and through breastfeeding by a drug-consuming mother. Prenatal exposure to cannabis has been associated with an altered rate of mental development and significant changes in nervous system functioning. However, the understanding of mechanisms of its action on developing the human CNS is still lacking. We investigated the effect of continuous exposure to cannabinoids on developing human neurons, mimicking the prenatal exposure by drug-consuming mother. Two human induced pluripotent stem cells (hiPSC) lines were induced to differentiate into neuronal cells and exposed for 37 days to cannabidiol (CBD), Δ9-THC, and two SCs, THJ-018 and EG-018. Both Δ9-THC and SC, at 10 μM, promote precocious neuronal and glial differentiation, while CBD at the same concentration is neurotoxic. Neurons exposed to Δ9-THC and SC show abnormal functioning of voltage-gated calcium channels when stimulated by extracellular potassium. In sum, all studied substances have a profound impact on the developing neurons, highlighting the importance of thorough research on the impact of prenatal exposure to natural and SC.application/pdfpt_PThiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiationPersonalMiranda, Cláudia C.DSpacehttp://dspace.org/items/8cbd2c5d-05a9-4ab8-8172-1466cdfe88aeDSpacehttp://dspace.org/items/8cbd2c5d-05a9-4ab8-8172-1466cdfe88aeMirandaCláudiaCiência IDhttps://www.ciencia-id.ptC519-E3D0-A3BFORCIDhttp://orcid.org0000-0001-8602-6014Researcher IDhttps://www.researcherid.comA-2966-2017Scopus Author IDhttps://www.scopus.com57190091677PersonalBarata, TiagoDSpacehttp://dspace.org/items/efc30894-6ec1-41fe-8027-ba8fb2eb1f4cDSpacehttp://dspace.org/items/efc30894-6ec1-41fe-8027-ba8fb2eb1f4cBarataTiagoORCIDhttp://orcid.org0000-0002-1483-7990PersonalVaz, Sandra H.DSpacehttp://dspace.org/items/b282e0fa-69eb-4079-8752-b7dd914f7745DSpacehttp://dspace.org/items/b282e0fa-69eb-4079-8752-b7dd914f7745Henriques VazSandra CristinaCiência IDhttps://www.ciencia-id.pt0E1C-952D-61BEORCIDhttp://orcid.org0000-0003-4258-9397Ferreira, CarlaPersonalQuintas, AlexandreDSpacehttp://dspace.org/items/4f377dfb-a56f-45a0-a480-80db151ffb89DSpacehttp://dspace.org/items/4f377dfb-a56f-45a0-a480-80db151ffb89QuintasAlexandreCiência IDhttps://www.ciencia-id.ptEF1A-A226-AC0FORCIDhttp://orcid.org0000-0002-5188-0453Scopus Author IDhttps://www.scopus.com6701600888PersonalBekman, EvgueniaDSpacehttp://dspace.org/items/73865db3-5b91-4a8f-8f89-bd8ec8e9ae61DSpacehttp://dspace.org/items/73865db3-5b91-4a8f-8f89-bd8ec8e9ae61BekmanEvgueniaCiência IDhttps://www.ciencia-id.pt6D1D-1265-F8B6ORCIDhttp://orcid.org0000-0002-3963-1358Researcher IDhttps://www.researcherid.comO-9840-2017Scopus Author IDhttps://www.scopus.com6602470751HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptDOIIsPartOf10.3389/fnmol.2020.001192022-06-06T14:41:39Z20202020-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/53284http://purl.org/coar/access_right/c_abf2open accessCBDEG-018THJ-018hiPSCNeuronal differentiationPhytocannabinoidsSynthetic cannabinoidsΔ9-THC5804932 bytesFundação para a Ciência e a TecnologiaMODULATION OF THE BIDIRECTIONAL COMMUNICATION BETWEEN NEURONS AND ASTROCYTES AT THE SYNAPSE: INFLUENCE OF BDNF AND P2 RECEPTORSCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaInstitute for Bioengineering and Biosciences6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871European CommissionImplementation of The Discoveries Centre for Regenerative and Precision Medicine, a new Centre of Excellence in PortugalH2020Crossref Funder IDhttp://doi.org/10.13039/501100008530literaturehttp://purl.org/coar/resource_type/c_6501journal article2020http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/e0b4249e-f4ae-4cef-a3a7-8b12a5fd7df6/downloadFrontiers in Molecular Neuroscience |
| spellingShingle | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation Miranda, Cláudia C. CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| status | SINGLETON |
| subject.fl_str_mv | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| title | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| title_full | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| title_fullStr | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| title_full_unstemmed | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| title_short | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| title_sort | hiPSC-based model of prenatal exposure to cannabinoids: effect on neuronal differentiation |
| topic | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| topic_facet | CBD EG-018 THJ-018 hiPSC Neuronal differentiation Phytocannabinoids Synthetic cannabinoids Δ9-THC |
| url | http://hdl.handle.net/10451/53284 |
| visible | 1 |