PMID- 36150422 OWN - NLM STAT- MEDLINE DCOM- 20221025 LR - 20221027 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 120 DP - 2023 Jan 10 TI - Investigating the "two-hit hypothesis": Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice. PG - 110642 LID - S0278-5846(22)00134-8 [pii] LID - 10.1016/j.pnpbp.2022.110642 [doi] AB - Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood. Mice were prenatally exposed to viral mimetic, poly I:C (5 mg/kg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mg/kg, intraperitoneal) or vehicle during adolescence (postnatal day [PND]28-45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus). Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both. These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Guma, Elisa AU - Guma E AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada; Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, Bethesda, MD, USA. Electronic address: elisa.guma@mail.mcgill.ca. FAU - Cupo, Lani AU - Cupo L AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada. FAU - Ma, Weiya AU - Ma W AD - Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada. FAU - Gallino, Daniel AU - Gallino D AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada. FAU - Moquin, Luc AU - Moquin L AD - Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada. FAU - Gratton, Alain AU - Gratton A AD - Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada. FAU - Devenyi, Gabriel A AU - Devenyi GA AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada. FAU - Chakravarty, M Mallar AU - Chakravarty MM AD - Computational Brain Anatomy Laboratory, Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Department of Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada. Electronic address: mallar.chakravarty@mcgill.ca. LA - eng GR - CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220921 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 7J8897W37S (Dronabinol) RN - 0 (Endocannabinoids) RN - 0 (Receptor, Cannabinoid, CB2) RN - 0 (Cannabinoid Receptor Agonists) RN - 0 (Hallucinogens) RN - O84C90HH2L (Poly I-C) SB - IM MH - Pregnancy MH - Animals MH - Mice MH - Female MH - Male MH - Humans MH - *Cannabis/adverse effects MH - Dronabinol/adverse effects MH - Endocannabinoids MH - Receptor, Cannabinoid, CB2 MH - Cannabinoid Receptor Agonists MH - *Hallucinogens MH - Poly I-C/toxicity MH - *Prenatal Exposure Delayed Effects OTO - NOTNLM OT - Adolescent cannabis use OT - Brain development OT - Environmental risk factors OT - Maternal immune activation OT - Neuropsychiatric disorders OT - Rodent magnetic resonance imaging EDAT- 2022/09/24 06:00 MHDA- 2022/10/26 06:00 CRDT- 2022/09/23 19:23 PHST- 2022/05/24 00:00 [received] PHST- 2022/09/14 00:00 [revised] PHST- 2022/09/16 00:00 [accepted] PHST- 2022/09/24 06:00 [pubmed] PHST- 2022/10/26 06:00 [medline] PHST- 2022/09/23 19:23 [entrez] AID - S0278-5846(22)00134-8 [pii] AID - 10.1016/j.pnpbp.2022.110642 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jan 10;120:110642. doi: 10.1016/j.pnpbp.2022.110642. Epub 2022 Sep 21.