载脂蛋白 E4、年龄和性别调节急性间歇性高碳酸血症-低氧引起的呼吸可塑性。
APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia.
机构信息
Breathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, 32603, USA.
Department of Physical Therapy, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
出版信息
Function (Oxf). 2023 Jun 13;4(5):zqad026. doi: 10.1093/function/zqad026. eCollection 2023.
RATIONALE
Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses.
OBJECTIVES
Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH).
METHODS
In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity () and neuronal plasticity (apolipoprotein E, ) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h) knock-in rats were performed to test causality.
RESULTS
AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for (i.e., /) compared to individuals with other genotypes ( = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age ( = 0.004). Additionally, age was inversely related with change in P0.1 ( = 0.007). In h knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than h controls ( < 0.05).
CONCLUSIONS
genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults.
ADDITION TO KNOWLEDGE BASE
AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, ), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.
背景
急性间歇性低氧（AIH）有望改善慢性脊髓损伤和神经退行性疾病患者的运动功能恢复。然而，AIH 的人体试验报告显示，个体反应存在显著差异。
目的
确定个体因素（例如遗传、年龄和性别），这些因素决定了健康成年人对优化的 AIH 方案（急性间歇性高碳酸低氧，AIHH）反应幅度的大小。
方法
在 17 名健康个体（年龄=27±5 岁）中，评估了个体因素与 AIHH 引起的膈神经运动诱发电位（MEP）幅度和吸气口腔阻断压（P0.1）变化幅度之间的关系。检测了与 AIH 诱导的膈神经运动可塑性（载脂蛋白 E）和神经元可塑性（载脂蛋白 E）相关机制相关的基因中的单核苷酸多态性（SNP）。还分析了 AIHH 诱导的可塑性随年龄和性别的变化。在人源化（h）敲入大鼠中进行了额外的实验，以验证因果关系。
结果
与其他 基因型（即 /）的个体相比，载脂蛋白 E 基因杂合子（即 /）的个体 AIHH 诱导的膈神经 MEP 幅度变化较小（=0.048），且其他测试的 SNP 也是如此。无论年龄大小，男性的膈神经 MEP 增强幅度均大于女性（=0.004）。此外，年龄与 P0.1 的变化呈负相关（=0.007）。在 h 敲入大鼠中，AIHH 诱导的膈神经运动可塑性明显低于 h 对照组（<0.05）。
结论
基因型、性别和年龄是健康成年人 AIHH 诱导呼吸运动可塑性的重要生物学决定因素。
知识增加
AIH 是一种新的康复策略，可诱导慢性脊髓损伤和/或神经退行性疾病患者呼吸和非呼吸运动系统的功能恢复。图 5 由于大多数 AIH 试验报告 AIH 结果存在相当大的个体间变异性，我们研究了可能破坏健康人对优化 AIH 方案（AIHH）反应的因素。我们证明，遗传学（特别是脂质转运蛋白，）、年龄和性别是 AIHH 诱导呼吸运动可塑性的重要生物学决定因素。
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