Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
Physiol Rep. 2023 Jan;11(2):e15587. doi: 10.14814/phy2.15587.
Diaphragm muscle (DIAm) motor units comprise a phrenic motor neuron (PhMN), the phrenic nerve and the muscle fibers innervated, with the size of PhMNs and axons characteristic of motor unit type. Smaller PhMNs and their axons comprise slow (type S) and fatigue-resistant (type FR) DIAm motor units, while larger PhMNs and their axons comprise more fatigable (type FF) motor units. With aging, we have shown a loss of larger PhMNs, consistent with selective atrophy of type IIx/IIb DIAm fibers and reduced maximum DIAm force. In the present study, we hypothesized that with aging there is a loss of larger myelinated phrenic α motor axons. Female and male young (6 months) and old (24 months) Fischer 344 rats were studied. PhMNs were retrogradely labeled by intrapleural injection of 488-conjugated CTB. The phrenic nerves were excised ~1 cm from the DIAm insertion and mounted in resin, and phrenic α motor axons were delineated based on size (i.e., >4 μm diameters). In older rats, the number of larger PhMNs and larger phrenic α motor axons were reduced. There were no differences in non-α axons. In addition, there was evidence of demyelination of larger phrenic α motor axons in older rats. Together, these findings are consistent with the selective age-related vulnerability of larger PhMNs and denervation of type FF motor units, which may underlie DIAm sarcopenia.
膈肌（DIAm）运动单位包括膈神经运动神经元（PhMN）、膈神经和其所支配的肌纤维，PhMN 的大小和轴突特征决定了运动单位的类型。较小的 PhMN 及其轴突组成了慢（S 型）和抗疲劳（FR 型）DIAm 运动单位，而较大的 PhMN 及其轴突组成了更容易疲劳（FF 型）的运动单位。随着年龄的增长，我们已经发现较大的 PhMN 数量减少，这与 IIx/IIb 型 DIAm 纤维的选择性萎缩和最大 DIAm 力量的减少一致。在本研究中，我们假设随着年龄的增长，较大的有髓膈神经α运动轴突会丢失。研究了雌性和雄性年轻（6 个月）和年老（24 个月）的 Fischer 344 大鼠。通过胸腔内注射 488 标记的 CTB 将 PhMN 逆行标记。从 DIAm 插入处切取约 1cm 的膈神经，并置于树脂中，根据大小（即>4μm 直径）描绘膈神经α运动轴突。在老年大鼠中，较大的 PhMN 和较大的膈神经α运动轴突数量减少。非-α 轴突没有差异。此外，老年大鼠的较大膈神经α运动轴突存在脱髓鞘的证据。综上所述，这些发现与较大的 PhMN 具有选择性的年龄相关性易损性以及 FF 型运动单位的失神经支配一致，这可能是 DIAm 肌少症的基础。
