RESUMEN
Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Many meta-analyses have suggested an etiological relationship between C/S delivery and autism spectrum disorders (ASDs). However, as a risk factor for ASDs, C/S delivery has not yet been well studied. Because C/S deliveries have been increasing, it is very important to investigate the causal association between C/S and ASDs. Here, using three approaches, we showed experimentally that C/S delivery induced ASD-like traits in offspring mice, and that some of these changes were ameliorated by one-time oxytocin (OXT) treatment. Treatment with OXT receptor antagonists before natural delivery also induced ASD-related behaviors. Moreover, wild-type mice born to OXT-KO dams showed similar changes. Thus, insufficient OXT exposure from dams to offspring during delivery may be a trigger for ASD-related behaviors.
Asunto(s)
Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/fisiopatología , Cesárea/efectos adversos , Oxitocina/efectos adversos , Oxitocina/farmacología , Animales , Trastorno del Espectro Autista/genética , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Oxitocina/genética , Factores de RiesgoRESUMEN
In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2-/- mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in Nrf2-/- mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2-/- mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2-/- mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2-/- mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2-/- mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2-/- mice after DE exposure. Our results suggested that Nrf2 reduces the risk of pulmonary disease via modulating the airway innate immune response caused by DE in mice.
