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首页> 外文期刊>Cell biology international. >De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin (?/?) (?/?) mice
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De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin (?/?) (?/?) mice

机译：De Novo Tetrahydrobiopterin生物合成在Parkin（β/α）的炎症纹状体中受损（？/？）小鼠

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Abstract Parkinson's disease (PD), the second‐most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta , resulting in motor impairment. Loss‐of‐function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin (?/?) ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS‐exposed parkin (?/?) mice. As expected, the LPS (0.33?mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin (?/?) and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up‐regulated in the LPS challenge, a well‐known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin (?/?) mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death.
机译：摘要帕金森病（PD），第二次普遍的神经退行性疾病，主要是神经变性的特征在于NIGRA Pars ComparaA，导致汽车损伤。 Parkin中的功能丧失是疾病早期疾病的主要原因。虽然啮齿动物在Parkin缺乏（Parkin（？/？）），但是与中央氧化应激和能量代谢缺乏有关的一些多巴胺能系统功能障碍，这些动物只显示炎症条件下的纽埃拉特毒性途径变性。本研究研究了挥霍二糖（LPS）诱导抗炎刺激对四氢萘屈（BH4）合成酶（De Novo和Salvage途径）的影响，因为该辅因子对于多巴胺合成至关重要。在LPS暴露的Parkin（β/β）小鼠的纹状体中研究了线粒体含量和建筑。正如预期的那样，LPS（0.33？mg / kg; i.p.）挑战受到了与少年Parkin（β）和wt小鼠的自发运动和社会互动。此外，基因型会影响少年调查的动力学。炎症情景没有诱导线粒体超微结构的明显变化;然而，它增加了线粒体的数量，其尺寸较小，并且激发了细胞器的蠕变分布。此外，BH4 De Novo生物合成途径未能在LPS挑战中上调，是其活化的众所周知的刺激。 LPS治疗增加了Sepiapterin还原酶（SPR）表达，表明挽救途径的补偿。这可能表明多巴胺合成在炎症条件下在Parkin（β/β）小鼠中受到损害。最后，这种情景损害了转录因子BDNF的纹状体表达，可能有利于细胞死亡。

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