Chronic intermittent hypoxia remodels catecholaminergic nerve innervation in mouse atria

被引:6
作者
Bizanti, Ariege [1 ]
Zhang, Yuanyuan [1 ]
Toledo, Zulema [1 ]
Bendowski, Kohlton T. [1 ]
Harden, Scott W. [1 ]
Mistareehi, Anas [1 ]
Chen, Jin [1 ]
Gozal, David [2 ]
Heal, Maci [3 ]
Christie, Richard [4 ]
Hunter, Peter J. [4 ]
Paton, Julian F. R. [5 ]
Cheng, Zixi Jack [1 ,6 ]
机构
[1] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL USA
[2] Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA
[3] MBF Biosci, Williston, VT USA
[4] Univ Auckland, Auckland Bioengn Inst, Auckland, New Zealand
[5] Univ Auckland, Manaaki Manawa the Ctr Heart Res, Dept Physiol, Auckland, New Zealand
[6] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, 4110 Libra Dr, Orlando, FL 32816 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2024年 / 602卷 / 01期
基金
美国国家卫生研究院;
关键词
atria; chronic intermittent hypoxia; heart; intrinsic cardiac ganglia; sympathetic axons; tyrosine hydroxylase; OBSTRUCTIVE SLEEP-APNEA; NUCLEUS AMBIGUUS PROJECTIONS; VAGAL AFFERENT INNERVATION; EPICARDIAL ADIPOSE-TISSUE; BLOOD-PRESSURE; NEUROMUSCULAR-JUNCTIONS; SYMPATHETIC ACTIVATION; TYROSINE-HYDROXYLASE; CARDIAC GANGLIA; HEART;
D O I
10.1113/JP284961
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Chronic intermittent hypoxia (CIH, a model for sleep apnoea) is a major risk factor for several cardiovascular diseases. Autonomic imbalance (sympathetic overactivity and parasympathetic withdrawal) has emerged as a causal contributor of CIH-induced cardiovascular disease. Previously, we showed that CIH remodels the parasympathetic pathway. However, whether CIH induces remodelling of the cardiac sympathetic innervation remains unknown. Mice (male, C57BL/6J, 2-3 months) were exposed to either room air (RA, 21% O-2) or CIH (alternating 21% and 5.7% O-2, every 6 min, 10 h day-1) for 8-10 weeks. Flat-mounts of their left and right atria were immunohistochemically labelled for tyrosine hydroxylase (TH, a sympathetic marker). Using a confocal microscope (or fluorescence microscope) and Neurlocudia 360 digitization and tracing system, we scanned both the left and right atria and quantitatively analysed the sympathetic axon density in both groups. The segmentation data was mapped onto a 3D mouse heart scaffold. Our findings indicated that CIH significantly remodelled the TH immunoreactive (-IR) innervation of the atria by increasing its density at the sinoatrial node, the auricles and the major veins attached to the atria (P < 0.05, n = 7). Additionally, CIH increased the branching points of TH-IR axons and decreased the distance between varicosities. Abnormal patterns of TH-IR axons around intrinsic cardiac ganglia were also found following CIH. We postulate that the increased sympathetic innervation may further amplify the effects of enhanced CIH-induced central sympathetic drive to the heart. Our work provides an anatomical foundation for the understanding of CIH-induced autonomic imbalance.
引用
收藏
页码:49 / 71
页数:23
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