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首页> 外文期刊>International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience >Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of mammalian neuromuscular synapses
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Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of mammalian neuromuscular synapses

机译：产前高纤维素血症诱导氧化应激并加速哺乳动物神经肌肉突触的“老化”

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Enhanced levels of homocysteine during pregnancy induce oxidative stress and contribute to many age-related diseases. In this study, we analyzed age-dependent synaptic modifications in developing neuromuscular synapses of rats with prenatal hyperhomocysteinemia (hHCY). One of the main findings indicate that the intensity and the timing of transmitter release in synapses of neonatal (P6 and P10) hHCY rats acquired features of matured synaptic transmission of adult rats. The amplitude and frequency of miniature end-plate currents (MEPCs) and evoked transmitter release were higher in neonatal hHCY animals compared to the control group. Analysis of the kinetics of neurotransmitter release demonstrated more synchronized release in neonatal rats with hHCY. At the same time lower release probability was observed in adults with hHCY. Spontaneous transmitter release in neonates with hHCY was inhibited by hydrogen peroxide (H2O2) whereas in controls this oxidant was effective only in adult animals indicating a higher susceptibility of motor nerve terminals to oxidative stress. The morphology and the intensity of endocytosis of synaptic vesicles in motor nerve endings was assessed using the fluorescence dye FM 1-43. Adult-like synapses were found in neonates with hHCY which were characterized by a larger area of presynaptic terminals compared to controls. No difference in the intensity of FM 1-43 fluorescence was observed between two groups of animals. Prenatal hHCY resulted in reduced muscle strength assessed by the Paw Grip Endurance test. Using biochemical assays we found an increased level of H2O2 and lipid peroxidation products in the diaphragm muscles of hHCY rats. This was associated with a lowered activity of superoxide dismutase and glutathione peroxidase. Our data indicate that prenatal hHCY induces oxidative stress and apparent faster functional and morphological "maturation" of motor synapses. Our results uncover synaptic mechanisms of disrupted muscle function observed in hHCY conditions which may contribute to the pathogenesis of motor neuronal diseases associated with enhanced level of homocysteine.
机译：妊娠期间的同型半胱氨酸水平诱导氧化应激，有助于许多年龄相关的疾病。在这项研究中，我们分析了在发育产前高管症（HHCy）的大鼠神经肌肉突触中的年龄依赖性突触修饰。其中一个主要研究结果表明，新生儿（P6和P10）Hhcy大鼠突触突触中发射器释放的强度和时序获得了成年大鼠成熟突触传播的特征。与对照组相比，新生儿HHCY动物的微型端板电流（MEPCS）和诱发发射器释放的幅度和频率较高。对神经递质释放的动力学分析显示在Hhcy中新生大鼠中的更多同步释放。同时，在具有Hhcy的成年人中观察到下释放概率。通过过氧化氢（H 2 O 2）抑制了Hhcy的新生儿中的自发发射器释放，而在对照中，该氧化剂仅在成年动物中有效，表明运动神经末端达到氧化应激的较高敏感性。使用荧光染料FM 1-43评估动机神经结束中突触囊泡内吞作用的形态和强度。与对照相比，在具有HHCy的新生儿中发现了成人样的突触，其特征在于较大的突触前终端面积。在两组动物之间观察到FM 1-43荧光强度的差异。产前Hhcy导致爪子握持耐久性测试评估的肌肉强度降低。使用生化测定，我们发现Hhcy大鼠隔膜肌中的H 2 O 2和脂质过氧化产物的水平增加。这与超氧化物歧化酶和谷胱甘肽过氧化物酶的降低的活性有关。我们的数据表明产前Hhcy诱导电动机突触的氧化应激和表观更快的功能和形态学“成熟”。我们的结果发现在HHCY条件下观察到破坏肌肉功能的突触机制，这可能有助于与增强的同型半胱氨酸水平相关的运动神经元疾病的发病机制。

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