PMID- 35970295 OWN - NLM STAT- MEDLINE DCOM- 20221013 LR - 20221021 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 160 DP - 2022 Nov TI - Prenatal exposure to Cannabis smoke induces early and lasting damage to the brain. PG - 105406 LID - S0197-0186(22)00131-0 [pii] LID - 10.1016/j.neuint.2022.105406 [doi] AB - Cannabis is the most widely used illegal drug during pregnancy, however, the effects of gestational exposure to Cannabis smoke (CS) on the central nervous system development remain uncharacterised. This study investigates the effects of maternal CS inhalation on brain function in the offspring. Pregnant mice were exposed daily to 5 min of CS during gestational days (GD) 5.5-17.5. On GD 18.5 half of the dams were euthanized for foetus removal. The offspring from the remaining dams were euthanized on postnatal days (PND) 20 and 60 for evaluation. Brain volume, cortex cell number, SOX2, histone-H3, parvalbumin, NeuN, and BDNF immunoreactivity were assessed in all groups. In addition, levels of NeuN, CB1 receptor, and BDNF expression were assessed and cortical primary neurons from rats were treated with Cannabis smoke extract (CSE) for assessment of cell viability. We found that male foetuses from the CS exposed group had decreased brain volume, whereas mice at PND 60 from the exposed group presented with increased brain volume. Olfactory bulb and diencephalon volume were found lower in foetuses exposed to CS. Mice at PND 60 from the exposed group had a smaller volume in the thalamus and hypothalamus while the cerebellum presented with a greater volume. Also, there was an increase in cortical BDNF immunoreactivity in CS exposed mice at PND 60. Protein expression analysis showed an increase in pro-BDNF in foetus brains exposed to CS. Mice at PND 60 presented an increase in mature BDNF in the prefrontal cortex (PFC) in the exposed group and a higher CB1 receptor expression in the PFC. Moreover, hippocampal NeuN expression was higher in adult animals from the exposed group. Lastly, treatment of cortical primary neurons with doses of CSE resulted in decreased cell viability. These findings highlight the potential negative neurodevelopmental outcomes induced by gestational CS exposure. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Benevenuto, Sarah G M AU - Benevenuto SGM AD - Department of Surgery, Sector of Anatomy, Faculty of Veterinary Medicine and Animal Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: s.gomenezes@gmail.com. FAU - Domenico, Marlise D AU - Domenico MD AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Yariwake, Victor Y AU - Yariwake VY AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Dias, Clarissa Tavares AU - Dias CT AD - Department of Biosciences, Laboratory of Neuroscience and Nutrition, Federal University of Sao Paulo/UNIFESP, Santos, SP, Brazil. FAU - Mendes-da-Silva, Cristiano AU - Mendes-da-Silva C AD - Department of Biosciences, Laboratory of Neuroscience and Nutrition, Federal University of Sao Paulo/UNIFESP, Santos, SP, Brazil. FAU - Alves, Nilmara de O AU - Alves NO AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Caumo, Sofia Ellen da S AU - Caumo SEDS AD - Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil. FAU - Vasconcellos, Perola AU - Vasconcellos P AD - Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil. FAU - Morais, Damila R AU - Morais DR AD - Shimadzu Brazil, Barueri, Sao Paulo, Brazil. FAU - Cardoso, Marilia S AU - Cardoso MS AD - Campinas Poison Control Center, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil. FAU - Ianicelli, Janaina AU - Ianicelli J AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Waked, Dunia AU - Waked D AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. FAU - Davey, Gavin P AU - Davey GP AD - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. FAU - Boylan, Fabio AU - Boylan F AD - School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland. FAU - Costa, Jose L AU - Costa JL AD - Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil. FAU - Veras, Mariana Matera AU - Veras MM AD - Department of Pathology, Laboratory of Experimental Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220812 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cannabinoid Receptor Agonists) RN - 0 (Hallucinogens) RN - 0 (Histones) RN - 0 (Illicit Drugs) RN - 0 (Parvalbumins) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Smoke) SB - IM MH - Animals MH - Brain/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cannabinoid Receptor Agonists/pharmacology MH - *Cannabis/adverse effects/metabolism MH - Female MH - *Hallucinogens MH - Histones/metabolism MH - *Illicit Drugs/adverse effects/metabolism MH - Male MH - Mice MH - Parvalbumins/metabolism MH - Pregnancy MH - *Prenatal Exposure Delayed Effects/chemically induced/metabolism MH - Rats MH - Receptor, Cannabinoid, CB1/metabolism MH - Smoke/adverse effects OTO - NOTNLM OT - Brain development OT - Cannabinoids OT - Cannabis smoke extract OT - Gestation OT - Neuron COIS- Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/08/16 06:00 MHDA- 2022/10/14 06:00 CRDT- 2022/08/15 19:25 PHST- 2022/01/31 00:00 [received] PHST- 2022/08/02 00:00 [revised] PHST- 2022/08/07 00:00 [accepted] PHST- 2022/08/16 06:00 [pubmed] PHST- 2022/10/14 06:00 [medline] PHST- 2022/08/15 19:25 [entrez] AID - S0197-0186(22)00131-0 [pii] AID - 10.1016/j.neuint.2022.105406 [doi] PST - ppublish SO - Neurochem Int. 2022 Nov;160:105406. doi: 10.1016/j.neuint.2022.105406. Epub 2022 Aug 12.