In Utero Exposure to Environmental Tobacco Smoke Increases Neuroinflammation in Offspring.

The embryonic stage is the most vulnerable period for congenital abnormalities. Due to its prolonged developmental course, the central nervous system (CNS) is susceptible to numerous genetic, epigenetic, and environmental influences. During embryo implantation, the CNS is more vulnerable to external influences such as environmental tobacco smoke (ETS), increasing the risk for delayed fetal growth, sudden infant death syndrome, and immune system abnormalities. This study aimed to evaluate the effects of in utero exposure to ETS on neuroinflammation in the offspring of pregnant mice challenged or not with lipopolysaccharide (LPS). After the confirmation of mating by the presence of the vaginal plug until offspring birth, pregnant C57BL/6 mice were exposed to either 3R4F cigarettes smoke (Kentucky University) or compressed air, twice a day (1h each), for 21 days. Enhanced glial cell and mixed cell cultures were prepared from 3-day-old mouse pups. After cell maturation, both cells were stimulated with LPS or saline. To inhibit microglia activation, minocycline was added to the mixed cell culture media 24 h before LPS challenge. To verify the influence of in utero exposure to ETS on the development of neuroinflammatory events in adulthood, a different set of 8-week-old animals was submitted to the Autoimmune Experimental Encephalomyelitis (EAE) model. The results indicate that cells from LPS-challenged pups exposed to ETS in utero presented high levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNFα) and decreased cell viability. Such a proinflammatory environment could modulate fetal programming by an increase in microglia and astrocytes miRNA155. This scenario may lead to the more severe EAE observed in pups exposed to ETS in utero.

Exposure to tobacco smoke during the early postnatal period modifies receptors and enzymes of the endocannabinoid system in the brainstem and striatum in mice.

Environmental tobacco smoke (ETS) exposure during brain development has been associated with several disorders, such as depression, anxiety, sudden infant death syndrome, and the predisposition to addiction. The endocannabinoid system plays an essential role in neuronal development. We investigated the effects of early postnatal ETS exposure on the endocannabinoid system in different brain regions. C57BL/6 J mice were exposed to ETS that was generated from 3R4F cigarettes from postnatal day 3 (P3) to P14. Receptors and enzymes of the endocannabinoid system were assessed in infancy, adolescence, and adulthood by Western blot. In the brainstem, ETS exposure decreased cannabinoid 1 (CB1) receptor, CB2 receptor, N-arachidonoyl phosphatidyl ethanol-specific phospholipase D (NAPE-PLD), and fatty acid amino hydrolase (FAAH) levels and increased in diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) levels during infancy and decreased CB2 and FAAH levels during adulthood. In the striatum, ETS decreased in the NAPE-PLD and MAGL levels and increased FAAH levels during infancy, increased FAAH levels during adolescence, and decreased NAPE-PLD levels during adulthood. The present findings indicate that exposure to ETS during a critical period of brain development can disturb the endocannabinoid system in the brainstem and striatum, regions that are involved in the pathogenesis of sudden infant death syndrome and the susceptibility to addiction.