SARAH GOMES DE MENEZES BENEVENUTO
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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conferenceObject Prenatal exposure to marijuana causes morphological retinal changes in mice(2020) ZANTUT, Paulo; VERAS, Mariana; TAKAHASHI, Walter; BENEVENUTO, Sarah; SAFATLE, Angelica; PECORA, Ricardo; SALDIVA, Paulo; DAMICO, Francisco Max- NEGATIVE EFFECTS OF SMOKING MARIJUANA DURING PREGNANCY ON THE PLACENTA: EXPERIMENTAL EVIDENCE(2019) VERAS, Mariana; BENEVENUTO, Sarah; TORRES, Janaina; YARIWAKE, Victor; MORAES, Thamires; SILVA, Iran
- Prenatal exposure to Cannabis smoke induces early and lasting damage to the brain(2022) BENEVENUTO, Sarah G. M.; DOMENICO, Marlise D.; YARIWAKE, Victor Y.; DIAS, Clarissa Tavares; MENDES-DA-SILVA, Cristiano; ALVES, Nilmara de O.; CAUMO, Sofia Ellen da S.; VASCONCELLOS, Perola; MORAIS, Damila R.; CARDOSO, Marilia S.; IANICELLI, Janaina; WAKED, Dunia; DAVEY, Gavin P.; BOYLAN, Fabio; COSTA, Jose L.; VERAS, Mariana MateraCannabis 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.
- Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice(2021) ZANTUT, Paulo Roberto Arruda; VERAS, Mariana Matera; BENEVENUTTO, Sarah Gomes Menezes; SAFATLE, Angelica Mendonca Vaz; PECORA, Ricardo Augusto; YARIWAKE, Victor Yuji; TORRES, Janaina Iannicelli; SAKUNO, Gustavo; MARTINS, Marco Antonio Garcia; BOLZAN, Aline Adriana; TAKAHASHI, Walter Yukihiko; SALDIVA, Paulo Hilario Nascimento; DAMICO, Francisco MaxBackground Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.