Efeitos da fumaça do cigarro e da nicotina no desenvolvimento do sistema visual de camundongos

Abstract

According to WHO, smoking kills more than seven million people each year and lead to more than $ 1.4 trillion in expenses by governments. Despite widespread disclosure of cigarette maltreatment during pregnancy, it is estimated that 20-23% of women in Brazil smoke during gestation. Although the neurotoxic effects of cigarette use on brain development are known, the mechanisms involved in this process remain largely unknown. Considering that the visual system is widely recognized as a model of neural circuitry used in the study of the development and plasticity of nerve connections, the investigation of the effects of cigarette use on the development of the visual system offers great potential to elucidate mechanisms related to deleterious effects during pregnancy. Thus, the central hypothesis of this study was that the exogenous introduction of nicotine and other components of cigarette smoke would interfere with the development and maturation of nerve connections in the visual system. Specifically, we evaluated the impact of pre-and peri-natal exposure of mice to smoking and oral nicotine on the development of retinal connections to the dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and olivary pretectal nucleus (OPN). Intraocular injections of the Alexa Fluor fluorophores conjugated cholera toxin B (CTB) subunit were done to visualize retinal ganglion cell projections in the dLGN, SC and OPN. Overall, our findings revealed that exposure to cigarette smoke or to nicotine via oral administration during development have a profound effect on the refinement of retinal projections in the studied regions. Moreover, such exposure led to an increase in the incidence of visual abnormalities, loss of body weight and early eye opening. Thus, we believe that our results confirm our hypothesis that the exogenous introduction of nicotine and other components of cigarette smoke interfere with the development and maturation of retinal connections in the visual system of mice. Moreover, our findings contribute to the vast literature on the adverse consequences of smoking exposure during brain development, which currently afflicts thousands of children in Brazil.