PMID- 34261013 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20220411 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 52 DP - 2021 Nov TI - A proof-of-concept study of maternal immune activation mediated induction of Toll-like receptor (TLR) and inflammasome pathways leading to neuroprogressive changes and schizophrenia-like behaviours in offspring. PG - 48-61 LID - S0924-977X(21)00268-6 [pii] LID - 10.1016/j.euroneuro.2021.06.009 [doi] AB - Infection, particularly prenatal infection, leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes that drive prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviours through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-6, TNF-alpha and IL-17A assessed after 24 hours were observed in both the poly (I:C) and LPS-treated rats, while IL-1beta was only elevated in LPS-treated rats, indicating MIA. The offspring of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviours, deficits in social behaviours and prepulse inhibition. The hippocampus of offspring rats showed increased expression of Tlr3, Tlr4, Nlrp3, Il1b, and Il18 of poly (I:C) and Tlr4, Nlrp3, Cas1, Il1b, and Il18 of LPS-treated dams. Furthermore, Tlr and inflammasome genes were associated with social deficits and impaired prepulse inhibition in offspring rats. The results suggest that MIA due to prenatal infection can trigger TLR and inflammasome pathways and enhances the risk of schizophrenia-like behaviours in the later stages of life of the offspring. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Talukdar, Pinku Mani AU - Talukdar PM AD - Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. FAU - Abdul, Fazal AU - Abdul F AD - Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. FAU - Maes, Michael AU - Maes M AD - Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia. FAU - Berk, Michael AU - Berk M AD - Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Orygen, The Centre of Excellence in Youth Mental Health, the Department of Psychiatry and the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia. FAU - Venkatasubramanian, Ganesan AU - Venkatasubramanian G AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. FAU - Kutty, Bindu M AU - Kutty BM AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. FAU - Debnath, Monojit AU - Debnath M AD - Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. Electronic address: monozeet@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210711 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Inflammasomes) RN - 0 (Interleukin-18) RN - 0 (Lipopolysaccharides) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - O84C90HH2L (Poly I-C) SB - IM MH - Animals MH - Behavior, Animal MH - Female MH - Inflammasomes MH - Interleukin-18 MH - Lipopolysaccharides/pharmacology MH - NLR Family, Pyrin Domain-Containing 3 Protein/genetics MH - Poly I-C/pharmacology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Sprague-Dawley MH - *Schizophrenia/metabolism MH - Toll-Like Receptor 4 MH - Toll-Like Receptors/genetics OTO - NOTNLM OT - Inflammasome OT - Maternal immune activation OT - Neuroprogression OT - Schizophrenia OT - Toll-like receptor COIS- Conflict of Interest MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier - all unrelated to this work. EDAT- 2021/07/15 06:00 MHDA- 2022/04/12 06:00 CRDT- 2021/07/14 20:09 PHST- 2021/04/21 00:00 [received] PHST- 2021/06/17 00:00 [revised] PHST- 2021/06/21 00:00 [accepted] PHST- 2021/07/15 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2021/07/14 20:09 [entrez] AID - S0924-977X(21)00268-6 [pii] AID - 10.1016/j.euroneuro.2021.06.009 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2021 Nov;52:48-61. doi: 10.1016/j.euroneuro.2021.06.009. Epub 2021 Jul 11.