Bendowski Kohlton, Zhang Yuanyuan, Bizanti Ariege, Nguyen Duyen, Nair Adhithyaa, Ma Jichao, Chen Jin, Cheng Zixi Jack
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
Auton Neurosci. 2025 Apr;258:103221. doi: 10.1016/j.autneu.2024.103221. Epub 2024 Nov 29.
Due to a lack of anatomical studies utilizing female specimens, it is unclear how the nociceptive innervation of the mouse heart compares between sexes. To address this, flat-mount preparations of the left and right atria of male and female mice were immunohistochemically labeled for calcitonin gene-related peptide (CGRP, a common marker for nociceptive nerves), imaged, and digitally traced in high quality. The results show that 1) A network of CGRP-IR axons densely innervated the right and left atria. Large nerve bundle entry points and regional concentration of CGRP-IR axons were similar in both sexes. 2) The detailed distribution of CGRP-IR bundles and axons were digitized and mapped using Arivis (Zeiss) Vision4D software. The general distribution patterns in male and female mice were comparable to one another. 3) The density of CGRP-IR axons in the sinoatrial (SA) node region (Male: 0.0258 μm/μm ± 0.003; Female: 0.0347 μm/μm ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm ± 0.001; Female: 0.0228 μm/μm ± 0.005) were not found to be significantly different. 4) The distance between adjacent varicosities in the auricle (Male: 4.049 μm ± 0.3; Female: 4.241 μm ± 0.34), SA node region (Male: 2.812 μm ± 0.21; Female: 3.352 μm ± 0.29), and AV node region (Male: 2.999 μm ± 0.3; Female: 3.526 μm ± 0.26) were not significantly different between sexes. 5) Likewise, maximum varicosity diameters in the auricle (Male: 0.5356 μm ± 0.04; Female: 0.5274 μm ± 0.03), SA node region (Male: 0.4714 μm ± 0.02; Female: 0.5634 μm ± 0.04), and AV node region (Male: 0.5103 μm ± 0.02; Female: 0.5103 μm ± 0.03) between male and female specimens were similar. Our data shows the comparable nature of the CGRP-IR axons in mouse atria in both sexes. Moreover, this is the first time we employed flat-mount preparations of whole atria to analyze the distribution of CGRP-IR axons in male and female mice.
由于缺乏利用雌性标本进行的解剖学研究，目前尚不清楚小鼠心脏的伤害性神经支配在性别上有何差异。为了解决这个问题，对雄性和雌性小鼠的左右心房进行了整装标本制备，通过免疫组织化学方法标记降钙素基因相关肽（CGRP，伤害性神经的常用标志物），进行成像，并进行高质量的数字追踪。结果表明：1）CGRP免疫反应性（CGRP-IR）轴突网络密集地支配着左右心房。两性的大神经束进入点和CGRP-IR轴突的区域集中情况相似。2）使用Arivis（蔡司）Vision4D软件对CGRP-IR束和轴突的详细分布进行数字化和绘图。雄性和雌性小鼠的总体分布模式彼此可比。3）窦房（SA）结区域（雄性：0.0258μm/μm±0.003；雌性：0.0347μm/μm±0.006）和房室（AV）结区域（雄性：0.0138μm/μm±0.001；雌性：0.0228μm/μm±0.005）的CGRP-IR轴突密度没有显著差异。4）耳廓（雄性：4.049μm±0.3；雌性：4.241μm±0.34）、SA结区域（雄性：2.812μm±0.21；雌性：3.352μm±0.29）和AV结区域（雄性：2.999μm±0.3；雌性：3.526μm±0.26）中相邻膨体之间的距离在两性之间没有显著差异。5）同样，雄性和雌性标本在耳廓（雄性：0.5356μm±0.04；雌性：0.5274μm±0.03）、SA结区域（雄性：0.4714μm±0.02；雌性：0.5634μm±0.04）和AV结区域（雄性：0.5103μm±0.02；雌性：0.5103μm±0.03）的最大膨体直径相似。我们的数据显示了两性小鼠心房中CGRP-IR轴突的可比性。此外，这是我们首次采用整个心房的整装标本制备来分析雄性和雌性小鼠中CGRP-IR轴突的分布。
