PMID- 38142918 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20240307 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 116 DP - 2024 Feb TI - Maternal selenium dietary supplementation alters sociability and reinforcement learning deficits induced by in utero exposure to maternal immune activation in mice. PG - 349-361 LID - S0889-1591(23)00406-3 [pii] LID - 10.1016/j.bbi.2023.12.024 [doi] AB - Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model. Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1beta and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward. This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Gillespie, Brendan AU - Gillespie B AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. FAU - Houghton, Michael J AU - Houghton MJ AD - Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, VIC 3168, Australia; Victorian Heart Institute, Monash University, Clayton, VIC 3168, Australia. FAU - Ganio, Katherine AU - Ganio K AD - Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia. FAU - McDevitt, Christopher A AU - McDevitt CA AD - Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia. FAU - Bennett, Daniel AU - Bennett D AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. FAU - Dunn, Ariel AU - Dunn A AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. FAU - Raju, Sharvada AU - Raju S AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. FAU - Schroeder, Anna AU - Schroeder A AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. Electronic address: schroanna@googlemail.com. FAU - Hill, Rachel A AU - Hill RA AD - Department of Psychiatry, Monash University, Clayton, VIC 3168, Australia. Electronic address: rachel.hill@monash.edu. FAU - Cardoso, Barbara R AU - Cardoso BR AD - Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, VIC 3168, Australia. Electronic address: barbara.cardoso@monash.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231223 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - H6241UJ22B (Selenium) RN - O84C90HH2L (Poly I-C) SB - IM MH - Mice MH - Animals MH - Female MH - Pregnancy MH - Male MH - Humans MH - Behavior, Animal/physiology MH - *Selenium/pharmacology MH - Placenta MH - *Autism Spectrum Disorder MH - Disease Models, Animal MH - Poly I-C/pharmacology MH - Dietary Supplements MH - *Prenatal Exposure Delayed Effects OTO - NOTNLM OT - Cognition OT - Maternal immune activation OT - Poly-I:C OT - Selenium OT - Sociability EDAT- 2023/12/25 00:42 MHDA- 2024/01/22 06:43 CRDT- 2023/12/24 19:29 PHST- 2023/09/04 00:00 [received] PHST- 2023/11/24 00:00 [revised] PHST- 2023/12/19 00:00 [accepted] PHST- 2024/01/22 06:43 [medline] PHST- 2023/12/25 00:42 [pubmed] PHST- 2023/12/24 19:29 [entrez] AID - S0889-1591(23)00406-3 [pii] AID - 10.1016/j.bbi.2023.12.024 [doi] PST - ppublish SO - Brain Behav Immun. 2024 Feb;116:349-361. doi: 10.1016/j.bbi.2023.12.024. Epub 2023 Dec 23.