Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPBENEVENUTO, Sarah G. M.DOMENICO, Marlise D.YARIWAKE, Victor Y.DIAS, Clarissa TavaresMENDES-DA-SILVA, CristianoALVES, Nilmara de O.CAUMO, Sofia Ellen da S.VASCONCELLOS, PerolaMORAIS, Damila R.CARDOSO, Marilia S.IANICELLI, JanainaWAKED, DuniaDAVEY, Gavin P.BOYLAN, FabioCOSTA, Jose L.VERAS, Mariana Matera2022-12-212022-12-212022NEUROCHEMISTRY INTERNATIONAL, v.160, article ID 105406, 15p, 20220197-0186https://observatorio.fm.usp.br/handle/OPI/50908Cannabis 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 immunoreac-tivity 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 vol-ume 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.engrestrictedAccessCannabinoidsGestationBrain developmentNeuronCannabis smoke extractpolycyclic aromatic-hydrocarbonsmarijuana smokeneurotrophic factorcb1 receptorsendocannabinoid systemcognitive-developmentneuronal developmentsubventricular zoneperinatal exposureadult ratsarticleCopyright PERGAMON-ELSEVIER SCIENCE LTD10.1016/j.neuint.2022.105406Biochemistry & Molecular BiologyNeurosciences1872-9754