Torcinaro Alessio, Ricci Valentina, Strimpakos Georgios, De Santa Francesca, Middei Silvia
Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), Via E. Ramarini, 00015 Rome, Italy.
European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy.
Brain Sci. 2021 Sep 20;11(9):1245. doi: 10.3390/brainsci11091245.
Sarcopenia, a geriatric syndrome involving loss of muscle mass and strength, is often associated with the early phases of Alzheimer's disease (AD). Pathological hallmarks of AD including amyloid β (Aβ) aggregates which can be found in peripheral tissues such as skeletal muscle. However, not much is currently known about their possible involvement in sarcopenia. We investigated neuronal innervation in skeletal muscle of Tg2576 mice, a genetic model for Aβ accumulation. We examined cholinergic innervation of skeletal muscle in adult Tg2576 and wild type mice by immunofluorescence labeling of tibialis anterior (TA) muscle sections using antibodies raised against neurofilament light chain (NFL) and acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (ChAT). Combining this histological approach with real time quantification of mRNA levels of nicotinic acetylcholine receptors, we demonstrated that in the TA of Tg2576 mice, neuronal innervation is significantly reduced and synaptic area is smaller and displays less ChAT content when compared to wild type mice. Our study provides the first evidence of reduced cholinergic innervation of skeletal muscle in a mouse model of Aβ accumulation. This evidence sustains the possibility that sarcopenia in AD originates from Aβ-mediated cholinergic loss.
肌肉减少症是一种涉及肌肉质量和力量丧失的老年综合征，常与阿尔茨海默病（AD）的早期阶段相关。AD的病理特征包括淀粉样β（Aβ）聚集体，这些聚集体可在骨骼肌等外周组织中发现。然而，目前对于它们可能参与肌肉减少症的情况知之甚少。我们研究了Tg2576小鼠骨骼肌中的神经支配，Tg2576小鼠是Aβ积累的遗传模型。我们通过使用针对神经丝轻链（NFL）和乙酰胆碱（ACh）合成酶胆碱乙酰转移酶（ChAT）的抗体对胫骨前肌（TA）肌肉切片进行免疫荧光标记，来检查成年Tg2576小鼠和野生型小鼠骨骼肌的胆碱能神经支配。将这种组织学方法与烟碱型乙酰胆碱受体mRNA水平的实时定量相结合，我们证明，与野生型小鼠相比，在Tg2576小鼠的TA中，神经支配显著减少，突触面积更小，ChAT含量更低。我们的研究首次证明了在Aβ积累的小鼠模型中骨骼肌胆碱能神经支配减少。这一证据支持了AD中的肌肉减少症源于Aβ介导的胆碱能丧失的可能性。
