Effects of Chronic Hypoxia on a Nonmammalian Vertebrate

描述(由申请人提供)：一些人类健康问题源于心血管和呼吸控制过程的功能障碍，这些过程已被慢性和/或间歇性低氧改变。这些因素包括婴儿猝死、胎儿和新生儿的发育影响、周期性呼吸、高血压、中风风险增加、心律失常以及各种心肺疾病的长期影响。哺乳动物对低氧的一些生理反应是适应旅居高海拔的。然而，一些反应的后果会导致病理。虽然在了解慢性和间歇性缺氧的影响方面已经取得了重大进展，但导致心血管和呼吸控制许多变化的神经机制仍然难以捉摸。此外，随着哺乳动物从胎儿到新生儿到成年的成熟，慢性缺氧的影响也发生了显著的变化。对有能力应对氧气供应的大规模、慢性和间歇性变化的动物进行调查，可能会让我们更好地了解人类疾病，或许还会有新的治疗策略。这项建议的总体目标是使用标准的生理测量和激光共聚焦显微镜来研究中枢和外周神经机制的变化，这些神经机制负责改变心血管和呼吸控制，以响应水呼吸通道叉尾鲨(Ictalurus Marktatus)的慢性和间歇性低氧。这项研究将填补我们对O2化学感受的一个关键空白。一些哺乳动物研究的战略性重复将使我们能够开始对脊椎动物的O2化学感受进行比较/系统发育分析。利用这种新的动物模型以及测定中枢和外周神经递质的身份和水平的其他实验可能会为O2化学接收的进化提供洞察力。

DESCRIPTION (provided by applicant): A number of human health problems stem from dysfunctional cardiovascular and ventilatory control processes which have been altered by chronic and/or intermittent hypoxia. These include SIDS, developmental effects in the fetus and neonate, periodic breathing, hypertension, increased risk for stroke, arrhythmias and the long-term effects of various cardio-pulmonary diseases. Some of the physiological responses of mammals to hypoxia are adaptive for sojourn to high altitudes. However, the consequences of some of the responses lead to pathologies. While there has been significant progress towards understanding the effects of chronic and intermittent hypoxia, the neural mechanisms responsible for many of the changes in cardiovascular and ventilatory control remain elusive. Also, significant changes occur in the effect of chronic hypoxia as a mammal matures from a fetus through neonate to adult. An investigation of animals that have the ability to routinely cope with large chronic and intermittent changes in O2 availability may lead the way to a better understanding of human diseases and perhaps novel treatment strategies. The overall objective of this proposal is to use standard physiological measurements and confocal laser microscopy to investigate changes in central and peripheral neural mechanisms responsible for altering cardiovascular and ventilatory control in response to chronic and intermittent hypoxia in the water-breathing channel catfish (Ictalurus punctatus). This study will fill a critical gap in our knowledge of O2 chemoreception. Strategic repetitions of some mammalian studies will allow a the beginning of a comparative/phylogenetic analysis of O2 chemoreception in vertebrates. Other experiments utilizing this novel animal model and the determination of central and peripheral neurotransmitter identities and levels may provide insight into the evolution of O2 chemoreception.