RT Journal Article
T1 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
A1 Romero Miguel, Diego
A1 Casquero-Veiga, Marta
A1 MacDowell, Karina S.
A1 Torres Sánchez, Sonia
A1 García Partida, José Antonio
A1 Lamanna Rama, Nicolás
A1 Romero Miranda, Ana
A1 Berrocoso, Esther
A1 Leza, Juan C.
A1 Desco Menéndez, Manuel
A1 Soto Montenegro, Mª Luisa
AB Background: 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.
PB OUP
SN 1461-1457
YR 2021
FD 2021-09
LK https://hdl.handle.net/10016/34419
UL https://hdl.handle.net/10016/34419
LA eng
NO M.L.S. was supported by the Ministerio de Ciencia, Innovación yUniversidades, Instituto de Salud Carlos III (projects PI14/00860and PI17/01766, and grant CPII14/00005), co-financed by EuropeanRegional Development Fund (ERDF), “A way of making Europe”,CIBER of Mental Health (CIBERSAM), Delegación del Gobiernopara el Plan Nacional sobre Drogas (2017/085), FundaciónMapfre and Fundación Alicia Koplowitz. M.C.-V. was supportedby Fundación Tatiana Pérez de Guzmán el Bueno. D.R.-M. wassupported 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 SanitariaGregorio Marañón. A.R.-M. was supported by Consejería deEducación e Investigación, Comunidad de Madrid, co-fundedby European Social Fund “Investing in your future” (grant,PEJ15/BIO/TL-0216). The CNIC was supported by the SpanishMinisterio de Ciencia, Innovación y Universidades (MCIU) andthe Pro-CNIC Foundation. J.C.L. was supported by the SpanishMinistry of Economy, Industry and Competitiveness (MINECOEU-FEDER) SAF2016-75500-R and CIBERSAM. E.B.D., S.T.-S., andJ.A.G.-P. were supported by grants: co-financed by the “FondoEuropeo de Desarrollo Regional” (FEDER)-UE “A way to buildEurope” 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 Nacionalsobre Drogas, Ministerio de Sanidad, Consumo y BienestarSocial” (2019I041); from the “Programa Operativo de AndalucíaFEDER, Iniciativa Territorial Integrada ITI 2014–2020 ConsejeríaSalud, Junta de Andalucía” (PI-0080-2017 and PI-0009-2017); fromthe Consejería de Salud de la Junta de Andalucía (PI-0134-2018);from the University of Cádiz (PR2019-046); from the “Institutode Investigación e Innovación en Ciencias Biomédicas deCádiz-INiBICA” (IN-C22; LI19/06IN-CO22); from the “Consejeríade Economía, Innovación, Ciencia y Empleo de la Junta deAndalucía” (CTS-510); from the “CIBERSAM” (CB/07/09/0033).
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RD 1 sept. 2024