Castro Paula Aiello Tomé de Souza, Faccioni Ludimila Canuto, Boer Patrícia Aline, Carvalho Robson Francisco, Matheus Selma Maria Michelin, Dal-Pai-Silva Maeli
Department of Physical Therapy, Center for Biologic Sciences and Health - CBSH, UFSCAR, São Carlos, São Paulo, Brazil.
Department of Morphology, UNESP Institute of Biosciences, Botucatu, São Paulo, Brazil.
Int J Exp Pathol. 2017 Apr;98(2):109-116. doi: 10.1111/iep.12229. Epub 2017 May 25.
Protein restriction during gestation can alter the skeletal muscle phenotype of offspring; however, little is known with regard to whether this also affects the neuromuscular junction (NMJ), as muscle phenotype maintenance depends upon NMJ functional integrity. This study aimed to evaluate the effects of a low protein (6%) intake by dams throughout gestation on male offspring NMJ morphology and nicotinic acetylcholine receptor (nAChR) α1, γ and ε subunit expression in the soleus (SOL) and extensor digitorum longus (EDL) muscles. Four groups of male Wistar offspring rats were studied. The offspring of dams fed low-protein (6% protein, LP) and normal protein (17% protein, NP) diets were evaluated at 30 and 120 days of age, and the SOL and EDL muscles were collected for analysis. Morphological studies using transmission electron microscopy revealed that only SOL NMJs were affected in 30-day-old offspring in the LP group compared with the NP group. SOL NMJs exhibited fewer synaptic folds, the postsynaptic membranes were smooth and myelin figures were also frequently observed in the terminal axons. With regard to the expression of mRNAs encoding nAChR subunits, only 30-day-old LP offspring EDL muscles exhibited reduced α, γ and ε subunit expression compared with the NP group. In conclusion, our results demonstrate that a low-protein diet (6%) imposed throughout pregnancy impairs the expression of mRNAs encoding the nAChR α, γ and ε subunits in EDL NMJs and promotes morphological changes in SOL NMJs of 30-day-old offspring, indicating specific differences among muscle types following long-term maternal protein restriction.
妊娠期蛋白质限制可改变后代骨骼肌表型;然而,关于这是否也会影响神经肌肉接头(NMJ),人们知之甚少,因为肌肉表型的维持依赖于NMJ的功能完整性。本研究旨在评估母鼠在整个妊娠期摄入低蛋白(6%)对雄性后代神经肌肉接头形态以及比目鱼肌(SOL)和趾长伸肌(EDL)中烟碱型乙酰胆碱受体(nAChR)α1、γ和ε亚基表达的影响。研究了四组雄性Wistar后代大鼠。对喂食低蛋白(6%蛋白质,LP)和正常蛋白(17%蛋白质,NP)日粮的母鼠所产后代在30日龄和120日龄时进行评估,并收集SOL和EDL肌肉进行分析。使用透射电子显微镜进行的形态学研究显示,与NP组相比,LP组30日龄后代中仅SOL神经肌肉接头受到影响。SOL神经肌肉接头的突触褶皱较少,突触后膜光滑,并且在轴突末端也经常观察到髓鞘样结构。关于编码nAChR亚基的mRNA表达,与NP组相比,仅30日龄LP后代的EDL肌肉中α、γ和ε亚基表达降低。总之,我们的结果表明,整个孕期摄入低蛋白饮食(6%)会损害EDL神经肌肉接头中编码nAChRα、γ和ε亚基的mRNA表达,并促进30日龄后代SOL神经肌肉接头的形态学变化,表明长期母体蛋白质限制后不同肌肉类型之间存在特定差异。