Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia
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 aime...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/4/970 |
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| author | Diego Romero-Miguel Marta Casquero-Veiga Javier Fernández Nicolás Lamanna-Rama Vanessa Gómez-Rangel Carlos Gálvez-Robleño Cristina Santa-Marta Claudio J. Villar Felipe Lombó Raquel Abalo Manuel Desco María Luisa Soto-Montenegro |
| author_facet | Diego Romero-Miguel Marta Casquero-Veiga Javier Fernández Nicolás Lamanna-Rama Vanessa Gómez-Rangel Carlos Gálvez-Robleño Cristina Santa-Marta Claudio J. Villar Felipe Lombó Raquel Abalo Manuel Desco María Luisa Soto-Montenegro |
| author_sort | Diego Romero-Miguel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:17:52Z |
| format | Article |
| id | doaj.art-4d96f283423242f4aa012b6548cc71bb |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T05:17:52Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-4d96f283423242f4aa012b6548cc71bb2023-11-17T18:07:00ZengMDPI AGAntioxidants2076-39212023-04-0112497010.3390/antiox12040970Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of SchizophreniaDiego Romero-Miguel0Marta Casquero-Veiga1Javier Fernández2Nicolás Lamanna-Rama3Vanessa Gómez-Rangel4Carlos Gálvez-Robleño5Cristina Santa-Marta6Claudio J. Villar7Felipe Lombó8Raquel Abalo9Manuel Desco10María Luisa Soto-Montenegro11Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainGrupo de Investigación “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, SpainInstituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainGrupo de Investigación de Alto Rendimiento en Fisiopatología y Farmacología del Sistema Digestivo (NeuGut-URJC), Universidad Rey Juan Carlos, 28922 Alcorcón, SpainDepartamento de Física Matemática y de Fluidos, Universidad Nacional de Educación a Distancia (UNED), 28040 Madrid, SpainGrupo de Investigación “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, SpainGrupo de Investigación “Biotechnology in Nutraceuticals and Bioactive Compounds-BIONUC”, Departamento de Biología Funcional, Área de Microbiología, Universidad de Oviedo, 33006 Oviedo, SpainGrupo de Investigación de Alto Rendimiento en Fisiopatología y Farmacología del Sistema Digestivo (NeuGut-URJC), Universidad Rey Juan Carlos, 28922 Alcorcón, SpainInstituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, SpainThe 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.https://www.mdpi.com/2076-3921/12/4/970Poly I:Cschizophreniamicrobiota-gut-brain axisinflammationoxidative stress |
| spellingShingle | Diego Romero-Miguel Marta Casquero-Veiga Javier Fernández Nicolás Lamanna-Rama Vanessa Gómez-Rangel Carlos Gálvez-Robleño Cristina Santa-Marta Claudio J. Villar Felipe Lombó Raquel Abalo Manuel Desco María Luisa Soto-Montenegro Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia Antioxidants Poly I:C schizophrenia microbiota-gut-brain axis inflammation oxidative stress |
| title | Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia |
| title_full | Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia |
| title_fullStr | Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia |
| title_full_unstemmed | Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia |
| title_short | Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia |
| title_sort | maternal supplementation with n acetylcysteine modulates the microbiota gut brain axis in offspring of the poly i c rat model of schizophrenia |
| topic | Poly I:C schizophrenia microbiota-gut-brain axis inflammation oxidative stress |
| url | https://www.mdpi.com/2076-3921/12/4/970 |
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