Fogarty Matthew J, Omar Tanya S, Zhan Wen-Zhi, Mantilla Carlos B, Sieck Gary C
Department of Physiology and Biomedical Engineering, Mayo Clinic , Rochester, Minnesota.
School of Biomedical Sciences, The University of Queensland , Brisbane , Australia.
J Neurophysiol. 2018 May 1;119(5):1852-1862. doi: 10.1152/jn.00868.2017. Epub 2018 Feb 7.
Sarcopenia is the age-related reduction of muscle mass and specific force. In previous studies, we found that sarcopenia of the diaphragm muscle (DIAm) is evident by 24 mo of age in both rats and mice and is associated with selective atrophy of type IIx and IIb muscle fibers and a decrease in maximum specific force. These fiber type-specific effects of sarcopenia resemble those induced by DIAm denervation, leading us to hypothesize that sarcopenia is due to an age-related loss of phrenic motor neurons (PhMNs). To address this hypothesis, we determined the number of PhMNs in young (6 mo old) and old (24 mo old) Fischer 344 rats. Moreover, we determined age-related changes in the size of PhMNs, since larger PhMNs innervate type IIx and IIb DIAm fibers. The PhMN pool was retrogradely labeled and imaged with confocal microscopy to assess the number of PhMNs and the morphometry of PhMN soma and proximal dendrites. In older animals, there were 22% fewer PhMNs, a 19% decrease in somal surface area, and a 21% decrease in dendritic surface area compared with young Fischer 344 rats. The age-associated loss of PhMNs involved predominantly larger PhMNs. These results are consistent with an age-related denervation of larger, more fatigable DIAm motor units, which are required primarily for high-force airway clearance behaviors. NEW & NOTEWORTHY Diaphragm muscle sarcopenia in rodent models is well described in the literature; however, the relationship between sarcopenia and frank phrenic motor neuron (MN) loss is unexplored in these models. We quantify a 22% loss of phrenic MNs in old (24 mo) compared with young (6 mo) Fischer 344 rats. We also report reductions in phrenic MN somal and proximal dendritic morphology that relate to decreased MN heterogeneity in old compared with young Fischer 344 rats.
肌肉减少症是与年龄相关的肌肉质量和比肌力的下降。在之前的研究中，我们发现大鼠和小鼠在24月龄时膈肌的肌肉减少症就很明显，并且与IIx型和IIb型肌纤维的选择性萎缩以及最大比肌力的降低有关。肌肉减少症的这些纤维类型特异性效应类似于膈肌去神经支配所诱导的效应，这使我们推测肌肉减少症是由于与年龄相关的膈运动神经元（PhMNs）丢失所致。为了验证这一假设，我们测定了年轻（6月龄）和年老（24月龄）的Fischer 344大鼠的PhMNs数量。此外，由于较大的PhMNs支配IIx型和IIb型膈肌纤维，我们还测定了与年龄相关的PhMNs大小的变化。通过逆行标记PhMN池并用共聚焦显微镜成像来评估PhMNs的数量以及PhMN胞体和近端树突的形态测量。与年轻的Fischer 344大鼠相比，老年动物的PhMNs数量减少了22%，胞体表面积减少了19%，树突表面积减少了21%。与年龄相关的PhMNs丢失主要涉及较大的PhMNs。这些结果与较大的、更易疲劳的膈肌运动单位与年龄相关的去神经支配一致，这些运动单位主要用于高力量的气道清理行为。新发现与值得注意的点：啮齿动物模型中膈肌肌肉减少症在文献中有很好的描述；然而，在这些模型中肌肉减少症与明显的膈运动神经元（MN）丢失之间的关系尚未被探索。我们量化了老年（24月龄）Fischer 344大鼠与年轻（6月龄）相比膈MNs减少了22%。我们还报告了与年轻的Fischer 344大鼠相比，老年大鼠膈MN胞体和近端树突形态的减少，这与老年大鼠MN异质性降低有关。
