>b<Efeitos da fumaça da >i<Cannabis sativa>/i< e de compostos Canabinóides>/b<: uma avaliação >i<in vivo>/i< e >i<in vitro>/i<

Abstract

The effects of maternal marijuana use on the development of central nervous system in offsprings are not completely understood. In this study, we have investigated the effects of maternal Cannabis smoke inhalation on the brain development and the effects of cannabinoids and Cannabis smoke extracts on in vitro mitochondrial function. Pregnant mice (n = 20) were exposed daily for 5 minutes to marijuana smoke (0.2 g of Cannabis), or filtered air from gestational day (GD) 5.5 to 17.5 GD. On GD 18.5 half of the dams (n=10) were euthanized and the other half (n=10) were euthanized at postnatal day (PND) 20 and 60 for stereological, immunohistochemical, and Western blotting analysis. Neurons culture from rats and differentiated PC12 cells were treated with AEA, THC, and CBD to assess cell viability and mitochondrial function (reactive oxygen species production i.e. ROS), membrane potential, and mitochondrial dynamic). PHAs, elemental composition, and cannabinoids characterization were carried out by using the particulate material and the drug, respectively. The animals exposed to marijuana smoke during gestation presented changes in encephalon total volume, thalamus, hypothalamus, and cerebellum at PND 60. There was an alteration in the volume of the olfactory bulb and the diencephalon in fetuses. The thickness of the cortical layers changed in animals with PND 20 and 60. There was an increase in BDNF in the cortex of adult animals and a change in the expression of BDNF proteins (GD18 and PND60), CB1, and NeuN (PND60). Also, sexspecific differences were found. Cell viability and membrane potential were decreased.On the other hand, increased ROS production was found, and inhibition of mitochondrial dynamics was observed in cell cultures. In summary, this study points out that smoke Cannabis exposure in vivo and in vitro may cause brain damage in mice and in neuronal mitochondrial function.