Departments of Psychiatry and Biobehavioral Sciences and Neurobiology, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California.
Institute for Cardiovascular and Metabolic Disease, University of North Texas Health Science Center, Fort Worth, Texas.
Am J Physiol Heart Circ Physiol. 2018 Feb 1;314(2):H270-H277. doi: 10.1152/ajpheart.00268.2017. Epub 2017 Nov 3.
ΔFosB is a member of the activator protein-1 family of transcription factors. ΔFosB has low constitutive expression in the central nervous system and is induced after exposure of rodents to intermittent hypoxia (IH), a model of the arterial hypoxemia that accompanies sleep apnea. We hypothesized ΔFosB in the nucleus of the solitary tract (NTS) contributes to increased mean arterial pressure (MAP) during IH. The NTS of 11 male Sprague-Dawley rats was injected (3 sites, 100 nl/site) with a dominant negative construct against ΔFosB (ΔJunD) in an adeno-associated viral vector (AAV)-green fluorescent protein (GFP) reporter. The NTS of 10 rats was injected with AAV-GFP as sham controls. Two weeks after NTS injections, rats were exposed to IH for 8 h/day for 7 days, and MAP was recorded using telemetry. In the sham group, 7 days of IH increased MAP from 99.8 ± 1.1 to 107.3 ± 0.5 mmHg in the day and from 104.4 ± 1.1 to 109.8 ± 0.6 mmHg in the night. In the group that received ΔJunD, IH increased MAP during the day from 95.9 ± 1.7 to 101.3 ± 0.4 mmHg and from 100.9 ± 1.7 to 102.8 ± 0.5 mmHg during the night (both IH-induced changes in MAP were significantly lower than sham, P < 0.05). After injection of the dominant negative construct in the NTS, IH-induced ΔFosB immunoreactivity was decreased in the paraventricular nucleus ( P < 0.05); however, no change was observed in the rostral ventrolateral medulla. These data indicate that ΔFosB within the NTS contributes to the increase in MAP induced by IH exposure. NEW & NOTEWORTHY The results of this study provides new insights into the molecular mechanisms that mediate neuronal adaptations during exposures to intermittent hypoxia, a model of the hypoxemias that occur during sleep apnea. These adaptations are noteworthy as they contribute to the persistent increase in blood pressure induced by exposures to intermittent hypoxia.
ΔFosB 是激活蛋白-1 家族转录因子的成员。ΔFosB 在中枢神经系统中的基础表达水平较低，在暴露于间歇性低氧（IH）后诱导产生，IH 是睡眠呼吸暂停伴随的动脉低氧血症的模型。我们假设，孤束核（NTS）中的 ΔFosB 有助于在 IH 期间增加平均动脉压（MAP）。11 只雄性 Sprague-Dawley 大鼠的 NTS 通过腺相关病毒（AAV）-绿色荧光蛋白（GFP）报告载体中的显性负性构建物（ΔJunD）在 3 个部位（100nl/部位）进行注射。10 只大鼠的 NTS 接受 AAV-GFP 注射作为假对照。NTS 注射后 2 周，大鼠每天接受 IH 暴露 8 小时，使用遥测法记录 MAP。在假对照组中，7 天的 IH 使白天的 MAP 从 99.8±1.1mmHg 增加到 107.3±0.5mmHg，夜间从 104.4±1.1mmHg 增加到 109.8±0.6mmHg。在接受 ΔJunD 的组中，白天的 IH 使 MAP 从 95.9±1.7mmHg 增加到 101.3±0.4mmHg，夜间从 100.9±1.7mmHg 增加到 102.8±0.5mmHg（两种情况下 IH 诱导的 MAP 变化均显著低于假对照组，P<0.05）。在 NTS 中注射显性负性构建物后，PVN 中的 IH 诱导的 ΔFosB 免疫反应性降低（P<0.05）；然而，在延髓头端腹外侧区未观察到变化。这些数据表明，NTS 内的 ΔFosB 有助于 IH 暴露引起的 MAP 增加。这项研究的结果为介导间歇性低氧暴露期间神经元适应的分子机制提供了新的见解，间歇性低氧是睡眠呼吸暂停期间发生的低氧血症模型。这些适应值得注意，因为它们有助于间歇性低氧暴露引起的血压持续升高。
