PMID- 32029751 OWN - NLM STAT- MEDLINE DCOM- 20201118 LR - 20210205 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Feb 6 TI - Effect of Immune Activation during Early Gestation or Late Gestation on Inhibitory Markers in Adult Male Rats. PG - 1982 LID - 10.1038/s41598-020-58449-x [doi] LID - 1982 AB - People with schizophrenia exhibit deficits in inhibitory neurons and cognition. The timing of maternal immune activation (MIA) may present distinct schizophrenia-like phenotypes in progeny. We investigated whether early gestation [gestational day (GD) 10] or late gestation (GD19) MIA, via viral mimetic polyI:C, produces deficits in inhibitory neuron indices (GAD1, PVALB, SST, SSTR2 mRNAs) within cortical, striatal, and hippocampal subregions of male adult rat offspring. In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing. FAU - Rahman, Tasnim AU - Rahman T AD - School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. AD - Neuroscience Research Australia, Sydney, NSW, Australia. FAU - Weickert, Cynthia Shannon AU - Weickert CS AD - School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. AD - Neuroscience Research Australia, Sydney, NSW, Australia. AD - Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY, USA. FAU - Harms, Lauren AU - Harms L AD - School of Psychology, The University of Newcastle, Sydney, NSW, Australia. AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Meehan, Crystal AU - Meehan C AD - School of Psychology, The University of Newcastle, Sydney, NSW, Australia. AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. AD - Division of Psychology, School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia. FAU - Schall, Ulrich AU - Schall U AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. AD - School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia. FAU - Todd, Juanita AU - Todd J AD - School of Psychology, The University of Newcastle, Sydney, NSW, Australia. AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Hodgson, Deborah M AU - Hodgson DM AD - School of Psychology, The University of Newcastle, Sydney, NSW, Australia. AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Michie, Patricia T AU - Michie PT AD - School of Psychology, The University of Newcastle, Sydney, NSW, Australia. AD - Priority Centre for Brain and Mental Health Research, The University of Newcastle, Newcastle, NSW, Australia. AD - Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Purves-Tyson, Tertia AU - Purves-Tyson T AD - School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. t.purves-tyson@neura.edu.au. AD - Neuroscience Research Australia, Sydney, NSW, Australia. t.purves-tyson@neura.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200206 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Il6 protein, rat) RN - 0 (Interleukin-6) RN - 0 (Receptors, Somatostatin) RN - 0 (Sstr2 protein, rat) RN - 51110-01-1 (Somatostatin) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) RN - O84C90HH2L (Poly I-C) SB - IM MH - Animals MH - Behavior, Animal MH - Biomarkers/analysis/metabolism MH - Cerebral Cortex/pathology MH - Corpus Striatum/pathology MH - Disease Models, Animal MH - Down-Regulation/immunology MH - Female MH - Glutamate Decarboxylase/analysis/metabolism MH - Hippocampus/pathology MH - Humans MH - Interleukin-6/analysis/metabolism MH - Interneurons/immunology/metabolism/pathology MH - Male MH - Neural Inhibition/*immunology MH - Poly I-C/immunology MH - Pregnancy MH - Pregnancy Complications, Infectious/*immunology MH - Prenatal Exposure Delayed Effects/*immunology MH - Rats MH - Receptors, Somatostatin/analysis/metabolism MH - Schizophrenia/*immunology/pathology MH - Sex Factors MH - Signal Transduction/immunology MH - Somatostatin/analysis/metabolism MH - Time Factors PMC - PMC7004984 COIS- C.S.W. is on an advisory board for Lundbeck, Australia Pty Ltd and in collaboration with Astellas Pharma Inc., Japan. The other authors declare that they have no competing interests. Funding sources had no involvement in study design, in the writing of the report, or in the decision to submit the manuscript for publication. All authors declare that they have no competing financial or non-financial interests in relation to the work described in this report. The funding sources did not have any influence on the design, data collection, and analyses of these data in conjunction with this work, or the writing of this manuscript, or in the decision to publish this work. EDAT- 2020/02/08 06:00 MHDA- 2020/11/20 06:00 PMCR- 2020/02/06 CRDT- 2020/02/08 06:00 PHST- 2019/07/31 00:00 [received] PHST- 2019/12/26 00:00 [accepted] PHST- 2020/02/08 06:00 [entrez] PHST- 2020/02/08 06:00 [pubmed] PHST- 2020/11/20 06:00 [medline] PHST- 2020/02/06 00:00 [pmc-release] AID - 10.1038/s41598-020-58449-x [pii] AID - 58449 [pii] AID - 10.1038/s41598-020-58449-x [doi] PST - epublish SO - Sci Rep. 2020 Feb 6;10(1):1982. doi: 10.1038/s41598-020-58449-x.