Mosher Bryan P, Taylor Barbara E, Harris Michael B
University of Alaska Fairbanks, Biology and Wildlife Department, Fairbanks, AK, United States.
University of Alaska Fairbanks, Biology and Wildlife Department, Fairbanks, AK, United States; Institute of Arctic Biology, Fairbanks, AK, United States.
Respir Physiol Neurobiol. 2014 Aug 15;200:33-9. doi: 10.1016/j.resp.2014.05.005. Epub 2014 May 27.
Serotonergic dysfunction compromises ventilatory chemosensitivity and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). We have shown raphé contributions to central chemosensitivity involving serotonin (5-HT)-and γ-aminobutyric acid (GABA)-mediated mechanisms. We tested the hypothesis that mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of GABA mechanisms. Rat pups were IHc-pretreated (eight consecutive cycles; 5 min 5% CO2 - air, 10 min air) or constant normocapnia-pretreated as a control, each day for 5 consecutive days beginning at P12. We subsequently assessed CO2 responsiveness using the in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. Results show IHc-pretreatment induces plasticity sufficient for responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. Responsiveness following IHc-pretreatment was absent if ketanserin was combined with GABAergic antagonism, indicating that plasticity depends on GABAergic mechanisms. We propose that IHc-induced plasticity could reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.
血清素能功能障碍会损害通气化学敏感性，并可能增加对诸如婴儿猝死综合征（SIDS）等疾病的易感性。我们已经表明中缝核在涉及5-羟色胺（5-HT）和γ-氨基丁酸（GABA）介导机制的中枢化学敏感性中发挥作用。我们检验了以下假设：轻度间歇性高碳酸血症（IHc）会诱导呼吸可塑性，部分原因是GABA机制的强化。从出生后第12天开始，将幼鼠连续5天每天进行IHc预处理（连续8个周期；5分钟5%二氧化碳-空气，10分钟空气）或持续常碳酸血症预处理作为对照。随后，我们使用原位灌注脑干标本评估二氧化碳反应性。在有和没有药理学操作的情况下测定高碳酸血症反应。结果显示，尽管去除了其他关键的酮色林敏感机制，但IHc预处理仍能诱导足以产生反应性的可塑性。如果将酮色林与GABA能拮抗作用相结合，IHc预处理后的反应性则不存在，这表明可塑性依赖于GABA能机制。我们提出，IHc诱导的可塑性可以降低诸如SIDS等疾病所潜在的反射功能障碍的严重程度。
