Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-04-07 DOI:10.1016/j.expneurol.2025.115240

Jayakrishnan Nair , Alexandria B. Marciante , Carter Lurk , Mia N. Kelly , Capron Maclain , Gordon S. Mitchell

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引用次数: 0

Abstract

Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Exposure to repetitive daily AIH (dAIH) enhances pLTF, a form of metaplasticity. Little is known concerning cellular mechanisms giving rise to dAIH-induced metaplasticity and the age-dependent sexual dimorphism of AIH associated pro-plasticity mRNA expression. To test if age, sex, and dAIH effects are associated with differential expression of molecules that regulate the Q- and S-pathways and their cross-talk interactions to phrenic motor facilitation, we analyzed key regulatory molecules in ventral spinal (C3-C5) homogenates from young (3-month) and middle-aged (12-month) male and female Sprague-Dawley rats. Since CNS estrogen levels impact molecules known to regulate the Q- and S-pathways, mRNA was correlated with serum estradiol. Rats (n = 8/group) were exposed to sham (21 % O2) or dAIH (15, 1 min episodes of 10.5 % inspired O2) per day for 14 days and sacrificed 24 h later. mRNAs for pLTF regulating molecules were assessed via RT-PCR, including: brain-derived neurotrophic factor (Bdnf); serotonin 2 A (Htr2a), 2B (Htr2b), and 7 (Htr7) receptors; adenosine 2a (Adora2a) receptors; exchange protein activated by cAMP (Epac1); p38 MAP kinase [Mapk14 (α) & Mapk11 (β)]; PKA regulatory (Prkar1a) and; catalytic subunits (Prkaa1); fractalkine (Cx3cl1), which underlies motor neuron/microglia communication; phosphodiesterase type 4b (Pde4b); NAPDH– gp91 (Cybb) and p47 (ncf1); and the PKC isoform, PKCδ (Prkcd). Here we report that age, sex, dAIH preconditioning, and estradiol influence molecules that initiate and/or regulate the Q- and S-pathways to phrenic motor facilitation.

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急性间歇性缺氧（AIH）会引起一种称为膈肌长期促进（pLTF）的呼吸运动可塑性。暴露于每天重复的 AIH（dAIH）会增强 pLTF，这是一种变态反应。人们对dAIH诱导的变态反应的细胞机制以及与AIH相关的促变态反应mRNA表达的年龄依赖性双态性知之甚少。为了测试年龄、性别和 dAIH 影响是否与调控 Q 和 S 通路的分子的不同表达及其与膈肌运动促进的交叉相互作用有关，我们分析了幼年（3 个月）和中年（12 个月）雌雄 Sprague-Dawley 大鼠腹侧脊髓（C3-C5）匀浆中的关键调控分子。由于中枢神经系统雌激素水平会影响已知的 Q 和 S 通路调控分子，因此 mRNA 与血清雌二醇相关。大鼠（n = 8只/组）每天暴露于假氧（21% O2）或dAIH（15次，每次1分钟，10.5%启发氧），持续14天，24小时后处死。通过 RT-PCR 对 pLTF 调控分子的 mRNA 进行了评估，包括脑源性神经营养因子 (Bdnf)；5-羟色胺 2 A (Htr2a)、2B (Htr2b) 和 7 (Htr7) 受体；腺苷 2a (Adora2a) 受体；cAMP 激活的交换蛋白 (Epac1)；p38 MAP 激酶 [Mapk14 (α) & Mapk11 (β)]；PKA调节亚基（Prkar1a）和催化亚基（Prkaa1）；支撑运动神经元/小胶质细胞通讯的分叉蛋白（Cx3cl1）；4b型磷酸二酯酶（Pde4b）；NAPDH- gp91（Cybb）和p47（ncf1）；以及PKC同工酶PKCδ（Prkcd）。在此，我们报告了年龄、性别、dAIH 预处理和雌二醇对启动和/或调节膈肌运动促进的 Q 和 S 通路的分子的影响。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.