PMID- 35286203 OWN - NLM STAT- MEDLINE DCOM- 20220420 LR - 20220915 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 119 IP - 12 DP - 2022 Mar 22 TI - Differential effects of early or late exposure to prenatal maternal immune activation on mouse embryonic neurodevelopment. PG - e2114545119 LID - 10.1073/pnas.2114545119 [doi] LID - e2114545119 AB - Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental and psychiatric disorders. MIA-induced deficits in adolescent and adult offspring have been well characterized; however, less is known about the effects of MIA exposure on embryo development. To address this gap, we performed high-resolution ex vivo MRI to investigate the effects of early (gestational day [GD]9) and late (GD17) MIA exposure on embryo (GD18) brain structure. We identify striking neuroanatomical changes in the embryo brain, particularly in the late-exposed offspring. We further examined the putative neuroanatomical underpinnings of MIA timing in the hippocampus using electron microscopy and identified differential effects due to MIA timing. An increase in apoptotic cell density was observed in the GD9-exposed offspring, while an increase in the density of neurons and glia with ultrastructural features reflective of increased neuroinflammation and oxidative stress was observed in GD17-exposed offspring, particularly in females. Overall, our findings integrate imaging techniques across different scales to identify differential impact of MIA timing on the earliest stages of neurodevelopment. FAU - Guma, Elisa AU - Guma E AUID- ORCID: 0000-0003-4651-8529 AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. AD - Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada. FAU - Bordeleau, Maude AU - Bordeleau M AD - Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada. AD - Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec City, QC G1V 4G2, Canada. FAU - Gonzalez Ibanez, Fernando AU - Gonzalez Ibanez F AUID- ORCID: 0000-0003-3330-437X AD - Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec City, QC G1V 4G2, Canada. AD - Departement de Medecine Moleculaire, Faculte de Medecine, Universite Laval, Quebec City, QC G1V 0A6, Canada. AD - Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada. FAU - Picard, Katherine AU - Picard K AD - Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec City, QC G1V 4G2, Canada. AD - Departement de Medecine Moleculaire, Faculte de Medecine, Universite Laval, Quebec City, QC G1V 0A6, Canada. AD - Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada. FAU - Snook, Emily AU - Snook E AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. AD - Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada. FAU - Desrosiers-Gregoire, Gabriel AU - Desrosiers-Gregoire G AUID- ORCID: 0000-0003-2197-1183 AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. AD - Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada. FAU - Spring, Shoshana AU - Spring S AD - Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. FAU - Lerch, Jason P AU - Lerch JP AD - Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. AD - Department of Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. AD - Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada. AD - Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford OX1 2JD, United Kingdom. FAU - Nieman, Brian J AU - Nieman BJ AD - Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. AD - Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada. AD - Translational Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. AD - Imaging Program, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. FAU - Devenyi, Gabriel A AU - Devenyi GA AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. AD - Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada. AD - Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V8P 5C2, Canada. FAU - Tremblay, Marie-Eve AU - Tremblay ME AD - Axe Neurosciences, Centre de Recherche du Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec City, QC G1V 4G2, Canada. AD - Departement de Medecine Moleculaire, Faculte de Medecine, Universite Laval, Quebec City, QC G1V 0A6, Canada. AD - Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada. AD - Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC V8P 5C2, Canada. AD - Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 0G4, Canada. FAU - Chakravarty, M Mallar AU - Chakravarty MM AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, QC H4H 1R3, Canada. AD - Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 0G4, Canada. AD - Department of Psychiatry, McGill University, Montreal, QC H3A 0G4, Canada. AD - Department of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, Canada. LA - eng GR - CIHR/Canada PT - Journal Article DEP - 20220314 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 SB - IM MH - Adolescent MH - Animals MH - *Autism Spectrum Disorder MH - Brain MH - Disease Models, Animal MH - Female MH - Humans MH - *Immune System/physiology MH - Inflammation MH - Magnetic Resonance Imaging MH - Mice MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - *Schizophrenia PMC - PMC8944668 OTO - NOTNLM OT - brain development OT - electron microscopy OT - embryo brain development OT - maternal immune activation OT - structural MRI COIS- The authors declare no competing interest. EDAT- 2022/03/15 06:00 MHDA- 2022/04/21 06:00 PMCR- 2022/09/14 CRDT- 2022/03/14 17:17 PHST- 2022/03/14 17:17 [entrez] PHST- 2022/03/15 06:00 [pubmed] PHST- 2022/04/21 06:00 [medline] PHST- 2022/09/14 00:00 [pmc-release] AID - 202114545 [pii] AID - 10.1073/pnas.2114545119 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2114545119. doi: 10.1073/pnas.2114545119. Epub 2022 Mar 14.