RT Journal Article T1 Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia A1 Romero Miguel, Luis Diego A1 Casquero-Veiga, Marta A1 Fernández, Javier A1 Lamanna Rama, Nicolás A1 Gómez Rangel, Vanessa A1 Gálvez-Robleño, Carlos A1 Santa Marta, Cristina A1 Villar, Claudio J. A1 Lombo, Felipe A1 Abalo, Raquel A1 Desco Menéndez, Manuel A1 Soto Montenegro, Mª Luisa AB The microbiota-gut-brain axis is a complex interconnected system altered in schizophrenia. The antioxidant N-acetylcysteine (NAC) has been proposed as an adjunctive therapy to antipsychotics in clinical trials, but its role in the microbiota-gut-brain axis has not been sufficiently explored. We aimed to describe the effect of NAC administration during pregnancy on the gut-brain axis in the offspring from the maternal immune stimulation (MIS) animal model of schizophrenia. Pregnant Wistar rats were treated with PolyI:C/Saline. Six groups of animals were studied according to the study factors: phenotype (Saline, MIS) and treatment (no NAC, NAC 7 days, NAC 21 days). Offspring were subjected to the novel object recognition test and were scanned using MRI. Caecum contents were used for metagenomics 16S rRNA sequencing. NAC treatment prevented hippocampal volume reduction and long-term memory deficits in MIS-offspring. In addition, MIS-animals showed lower bacterial richness, which was prevented by NAC. Moreover, NAC7/NAC21 treatments resulted in a reduction of proinflammatory taxons in MIS-animals and an increase in taxa known to produce anti-inflammatory metabolites. Early approaches, like this one, with anti-inflammatory/anti-oxidative compounds, especially in neurodevelopmental disorders with an inflammatory/oxidative basis, may be useful in modulating bacterial microbiota, hippocampal size, as well as hippocampal-based memory impairments. PB MDPI SN 2076-3921 YR 2023 FD 2023-04-20 LK https://hdl.handle.net/10016/38869 UL https://hdl.handle.net/10016/38869 LA eng NO M.L.S.-M. was supported by the Ministerio de Ciencia e Innovación, Instituto de SaludCarlos III (project number PI17/01766, and grant number BA21/00030), co-financed by the EuropeanRegional Development Fund (ERDF), “A way to make Europe”; project PID2021-128862OB-I00funded by MCIN/AEI/10.13039/501100011033/FEDER, UE, CIBER de Salud Mental-Instituto deSalud Carlos III (project number CB07/09/0031); Delegación del Gobierno para el Plan Nacionalsobre Drogas (project number 2017/085, 2022/008917); and Fundación Alicia Koplowitz. D.R.-M.was supported by Consejería de Educación e investigación, Comunidad de Madrid, co-funded bythe European Social Fund “Investing in your future” (grant, PEJD-2018-PRE/BMD-7899). M.C.-V.was supported by a predoctoral grant from Fundación Tatiana Pérez de Guzmán el Bueno. N.L.-R.was supported by the Instituto de investigación Sanitaria Gregorio Marañón, “Programa Intramuralde Impulso a la I+D+I 2019”. V.G.-R was supported by Consejería de Educación e investigación,Comunidad de Madrid, co-funded by the European Social Fund “Investing in your future” (grant,PEJD-2017-TL/BMD-7385). C.G.-R. was supported by Universidad Rey Juan Carlos (PREDOC20-054). R.A. was supported by Ministerio de Ciencia, Innovación y Universidades (grant numberPID2019-111510RB-I00) and Grupo Español de Motilidad Digestiva (Beca Allergan, 2017). M.D. workwas supported by Ministerio de Ciencia e Innovación (MCIN) and Instituto de Salud Carlos III(PT20/00044). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministeriode Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center ofExcellence (SEV-2015-0505). J.F. was supported by “Contrato Intramural Postdoctoral” from FINBA(Principado de Asturias, Spain). F.L. was supported by Ayudas para grupos de investigación deorganismos del Principado de Asturias (SV-PA-21-AYUD/2021/51347). DS e-Archivo RD 30 jun. 2024