Nicotine or ethanol exposure early in development are both risk factors for Sudden Infant Death Syndrome (SIDS). I tested the hypothesis that both nicotine and ethanol may be linked to SIDS by impairing central breathing control responses to low oxygen (hypoxia) and high carbon dioxide (hypercapnia) stressors. Experiments were conducted in bullfrog tadpoles, a model system for respiratory neurotoxicology research. I addressed three specific aims: to characterize the effect of chronic ethanol on central responses to hypercapnia and hypoxia, to characterize the effect of chronic nicotine on central hypoxic responses, and to determine the persistence of hypercapnic impairments following 10-wk exposure to either nicotine or ethanol. 10-wk nicotine exposure resulted in neuroplastic changes that eliminated the central hypoxic responses of early but not late metamorphic tadpoles. Thus, central responses to both hypoxia and hypercapnia were impaired following nicotine exposure. The attenuated central hypercapnic response of nicotine-exposed tadpoles persisted for 1 - 3 wk. Following 10-wk chronic ethanol exposure central responses to hypercapnia and hypoxia were lost regardless of the developmental timing of exposure. Impairments in central hypercapnic responses persisted for 3 - 6 wk after ethanol exposure ended. The recovery of central hypercapnic responses in nicotine- and ethanol-exposed tadpoles may be an example of recuperative neuroplasticity resulting in either a reinstatement of network components and functions or an accommodation to deleterious nicotine- and ethanol-evoked neuroplastic changes. Collectively these data suggest that both nicotine and ethanol may target adaptive and compensatory mechanisms in central breathing control. The teratogen-induced impairments were developmentally dependent in the case of nicotine, and they persisted longer following ethanol exposure. The overall result of exposure to either neuroteratogen was an inability to respond to central breathing stressors, supporting the possible link to SIDS.
Thesis (Ph.D.) University of Alaska Fairbanks, 2010
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