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A Characterization of the Effects of Minocycline Treatment during Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders

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dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Biomedical Imaging and Instrumentation Groupes
dc.contributor.authorRomero Miguel, Diego
dc.contributor.authorCasquero-Veiga, Marta
dc.contributor.authorMacDowell, Karina S.
dc.contributor.authorTorres Sánchez, Sonia
dc.contributor.authorGarcía Partida, José Antonio
dc.contributor.authorLamanna Rama, Nicolás
dc.contributor.authorRomero Miranda, Ana
dc.contributor.authorBerrocoso, Esther
dc.contributor.authorLeza, Juan C.
dc.contributor.authorDesco Menéndez, Manuel
dc.contributor.authorSoto Montenegro, Mª Luisa
dc.contributor.funderComunidad de Madrides
dc.contributor.funderEuropean Commissionen
dc.contributor.funderMinisterio de Economía y Competitividad (España)es
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es
dc.contributor.funderUniversidad Carlos III de Madrides
dc.date.accessioned2022-03-18T11:48:31Z
dc.date.available2022-03-18T11:48:31Z
dc.date.issued2021-09
dc.description.abstractBackground: Minocycline (MIN) is a tetracycline with antioxidant, anti-inflammatory, and neuroprotective properties. Given the likely involvement of inflammation and oxidative stress (IOS) in schizophrenia, MIN has been proposed as a potential adjuvant treatment in this pathology. We tested an early therapeutic window, during adolescence, as prevention of the schizophrenia-related deficits in the maternal immune stimulation (MIS) animal model. Methods: On gestational day 15, Poly I:C or vehicle was injected in pregnant Wistar rats. A total 93 male offspring received MIN (30 mg/kg) or saline from postnatal day (PND) 35-49. At PND70, rats were submitted to the prepulse inhibition test. FDG-PET and T2-weighted MRI brain studies were performed at adulthood. IOS markers were evaluated in frozen brain tissue. Results: MIN treatment did not prevent prepulse inhibition test behavioral deficits in MIS offspring. However, MIN prevented morphometric abnormalities in the third ventricle but not in the hippocampus. Additionally, MIN reduced brain metabolism in cerebellum and increased it in nucleus accumbens. Finally, MIN reduced the expression of iNOS (prefrontal cortex, caudate-putamen) and increased the levels of KEAP1 (prefrontal cortex), HO1 and NQO1 (amygdala, hippocampus), and HO1 (caudate-putamen). Conclusions: MIN treatment during adolescence partially counteracts volumetric abnormalities and IOS deficits in the MIS model, likely via iNOS and Nrf2-ARE pathways, also increasing the expression of cytoprotective enzymes. However, MIN treatment during this peripubertal stage does not prevent sensorimotor gating deficits. Therefore, even though it does not prevent all the MIS-derived abnormalities evaluated, our results suggest the potential utility of early treatment with MIN in other schizophrenia domains.en
dc.description.sponsorshipM.L.S. was supported by the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III (projects PI14/00860 and PI17/01766, and grant CPII14/00005), co-financed by European Regional Development Fund (ERDF), “A way of making Europe”, CIBER of Mental Health (CIBERSAM), Delegación del Gobierno para el Plan Nacional sobre Drogas (2017/085), Fundación Mapfre and Fundación Alicia Koplowitz. M.C.-V. was supported by Fundación Tatiana Pérez de Guzmán el Bueno. D.R.-M. was supported by Consejería de Educación e Investigación, Comunidad de Madrid, co-funded by European Social Fund “Investing in your future” (grant, PEJD-2018-PRE/BMD-7899). N.L.-R. was supported by Instituto de investigación Sanitaria Gregorio Marañón. A.R.-M. was supported by Consejería de Educación e Investigación, Comunidad de Madrid, co-funded by European Social Fund “Investing in your future” (grant, PEJ15/BIO/TL-0216). The CNIC was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) and the Pro-CNIC Foundation. J.C.L. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECOEU- FEDER) SAF2016-75500-R and CIBERSAM. E.B.D., S.T.-S., and J.A.G.-P. were supported by grants: co-financed by the “Fondo Europeo de Desarrollo Regional” (FEDER)-UE “A way to build Europe” from the “Ministerio de Economía y Competitividad” (MINECO: RTI2018-099778-B-I00) and the “Ministerio de Salud- Instituto de Salud Carlos III (PI18/01691); from the “Plan Nacional sobre Drogas, Ministerio de Sanidad, Consumo y Bienestar Social” (2019I041); from the “Programa Operativo de Andalucía FEDER, Iniciativa Territorial Integrada ITI 2014–2020 Consejería Salud, Junta de Andalucía” (PI-0080-2017 and PI-0009-2017); from the Consejería de Salud de la Junta de Andalucía (PI-0134-2018); from the University of Cádiz (PR2019-046); from the “Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz-INiBICA” (IN-C22; LI19/06IN-CO22); from the “Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía” (CTS-510); from the “CIBERSAM” (CB/07/09/0033).en
dc.format.extent14
dc.identifier.bibliographicCitationRomero-Miguel, D., Casquero-Veiga, M., MacDowell, K. S., Torres-Sanchez, S., Garcia-Partida, J. A., Lamanna-Rama, N., Romero-Miranda, A., Berrocoso, E., Leza, J. C., Desco, M., & Soto-Montenegro, M. L. (2021). A Characterization of the Effects of Minocycline Treatment During Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disorders. In International Journal of Neuropsychopharmacology (Vol. 24, Issue 9, pp. 734–748). Oxford University Press (OUP).en
dc.identifier.doihttps://doi.org/10.1093/ijnp/pyab036
dc.identifier.issn1461-1457
dc.identifier.publicationfirstpage734
dc.identifier.publicationissue9
dc.identifier.publicationlastpage748
dc.identifier.publicationtitleInternational Journal of Neuropsychopharmacologyen
dc.identifier.publicationvolume24
dc.identifier.urihttps://hdl.handle.net/10016/34419
dc.identifier.uxxiAR/0000028882
dc.language.isoengen
dc.publisherOUPen
dc.relation.projectIDGobierno de España. Proyecto PI14/00860. Grant CPII14/00005es
dc.relation.projectIDUniversidad Carlos III de Madrid. Proyecto PI17/01766. Grant CPII14/00005es
dc.relation.projectIDComunidad de Madrid. PEJD-2018-PRE/BMD-7899es
dc.relation.projectIDComunidad de Madrid. PEJ15/BIO/TL-0216es
dc.relation.projectIDGobierno de España. SAF2016-75500-Res
dc.relation.projectIDGobierno de España. RTI2018-099778-B-I00es
dc.relation.projectIDUniversidad Carlos III de Madrid. PI18/01691es
dc.relation.projectIDGobierno de España. 2019I041es
dc.rights© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.en
dc.rightsAtribución-NoComercial 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/es/*
dc.subject.otherFdg-peten
dc.subject.otherInflammatory/oxidonitrosative stressen
dc.subject.otherMinocyclineen
dc.subject.otherPoly I:Cen
dc.subject.otherSchizophreniaen
dc.titleA Characterization of the Effects of Minocycline Treatment during Adolescence on Structural, Metabolic, and Oxidative Stress Parameters in a Maternal Immune Stimulation Model of Neurodevelopmental Brain Disordersen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
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