PMID- 38191622 OWN - NLM STAT- MEDLINE DCOM- 20240110 LR - 20240111 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 14 IP - 1 DP - 2024 Jan 8 TI - N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia. PG - 14 LID - 10.1038/s41398-023-02652-7 [doi] LID - 14 AB - Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15-21); and 3) NAC treatment throughout all pregnancy (GD1-21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder. CI - (c) 2024. The Author(s). FAU - Romero-Miguel, Diego AU - Romero-Miguel D AUID- ORCID: 0000-0002-8385-7936 AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, 28007, Spain. AD - Department of Bioengineering, Universidad Carlos III de Madrid, Leganes (Madrid), 28911, Spain. FAU - Casquero-Veiga, Marta AU - Casquero-Veiga M AUID- ORCID: 0000-0003-0859-9495 AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, 28007, Spain. AD - Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, IIS-FJD, 28040, Madrid, Spain. AD - Cardiovascular Imaging and Population Studies, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain. FAU - Lamanna-Rama, Nicolas AU - Lamanna-Rama N AUID- ORCID: 0000-0002-3450-566X AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, 28007, Spain. AD - Department of Bioengineering, Universidad Carlos III de Madrid, Leganes (Madrid), 28911, Spain. FAU - Torres-Sanchez, Sonia AU - Torres-Sanchez S AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. AD - Neuropsychopharmacology & Psychobiology Research Group, Department of Neuroscience, Universidad de Cadiz, Cadiz, 11003, Spain. AD - Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA), Hospital Universitario Puerta del Mar, Cadiz, 11009, Spain. FAU - MacDowell, Karina S AU - MacDowell KS AUID- ORCID: 0000-0002-1527-8895 AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. AD - Department of Pharmacology & Toxicology, School of Medicine, Universidad Complutense (UCM), IIS Imas12, IUIN, Madrid, 28040, Spain. FAU - Garcia-Partida, Jose A AU - Garcia-Partida JA AUID- ORCID: 0000-0002-9625-6718 AD - Neuropsychopharmacology & Psychobiology Research Group, Department of Neuroscience, Universidad de Cadiz, Cadiz, 11003, Spain. AD - Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA), Hospital Universitario Puerta del Mar, Cadiz, 11009, Spain. FAU - Santa-Marta, Cristina AU - Santa-Marta C AD - Department of Mathematical and Fluids Physics, UNED, Madrid, 28040, Spain. FAU - Berrocoso, Esther AU - Berrocoso E AUID- ORCID: 0000-0003-0208-7472 AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. AD - Neuropsychopharmacology & Psychobiology Research Group, Department of Neuroscience, Universidad de Cadiz, Cadiz, 11003, Spain. AD - Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA), Hospital Universitario Puerta del Mar, Cadiz, 11009, Spain. FAU - Leza, Juan C AU - Leza JC AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. AD - Department of Pharmacology & Toxicology, School of Medicine, Universidad Complutense (UCM), IIS Imas12, IUIN, Madrid, 28040, Spain. FAU - Desco, Manuel AU - Desco M AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, 28007, Spain. desco@hggm.es. AD - Department of Bioengineering, Universidad Carlos III de Madrid, Leganes (Madrid), 28911, Spain. desco@hggm.es. AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. desco@hggm.es. AD - Advanced Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, 28029, Spain. desco@hggm.es. FAU - Soto-Montenegro, Maria Luisa AU - Soto-Montenegro ML AUID- ORCID: 0000-0003-4350-4789 AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, 28007, Spain. marisa@hggm.es. AD - CIBER de Salud Mental (CIBERSAM), Madrid, 28029, Spain. marisa@hggm.es. AD - Grupo de Fisiopatologia y Farmacologia del Sistema Digestivo de la Universidad Rey Juan Carlos (NeuGut), Alcorcon (Madrid), 28922, Spain. marisa@hggm.es. LA - eng PT - Journal Article DEP - 20240108 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - WYQ7N0BPYC (Acetylcysteine) RN - O84C90HH2L (Poly I-C) SB - IM MH - Female MH - Pregnancy MH - Rats MH - Animals MH - Rats, Wistar MH - *Acetylcysteine/pharmacology MH - *Schizophrenia/drug therapy/prevention & control MH - Poly I-C MH - Inflammation PMC - PMC10774365 COIS- The authors declare no competing interests. EDAT- 2024/01/09 00:42 MHDA- 2024/01/10 06:42 PMCR- 2024/01/08 CRDT- 2024/01/08 23:51 PHST- 2023/04/04 00:00 [received] PHST- 2023/11/06 00:00 [accepted] PHST- 2023/10/24 00:00 [revised] PHST- 2024/01/10 06:42 [medline] PHST- 2024/01/09 00:42 [pubmed] PHST- 2024/01/08 23:51 [entrez] PHST- 2024/01/08 00:00 [pmc-release] AID - 10.1038/s41398-023-02652-7 [pii] AID - 2652 [pii] AID - 10.1038/s41398-023-02652-7 [doi] PST - epublish SO - Transl Psychiatry. 2024 Jan 8;14(1):14. doi: 10.1038/s41398-023-02652-7.