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Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

机译:腺苷酸环酶激活剂咳嗽可缓解颅内神经丙酸诱导自闭症大鼠的线粒体功能障碍

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Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations, which are major neuropathological hallmarks responsible for autism. Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate. Rat models of autism were established by intracerebroventricular injection of propionic acid. These rat models had memory dysfunction, decreased muscle coordination and gait imbalance. Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines, oxidative stress and lipid biomarkers. Oral administration of 10, 20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner. These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism. This study was approved by the RITS/IAEC, SIRSA, HARYANA on March 3, 2014 (approval No. RITS/IAEC/2014/03/03).
机译:神经元线粒体功能障碍增加炎症介质并导致自由基产生和抗氧化酶改变,这是负责自闭症的主要神经病理标志。由于单磷酸的循环腺苷水平降低,自闭症中的线粒体功能障碍与ATP水平降低有关。通过脑内注射丙酸建立了自闭症的大鼠模型。这些大鼠模型具有内存功能障碍,降低肌肉协调和步态不平衡。丙酸处理的大鼠的生化估计显示神经元线粒体电子传输链复合物中酶活性的变化,增加促炎细胞因子,氧化应激和脂质生物标志物。口服给药10,20和30mg / kg腺苷酸环酸酯环酶激活剂25天以剂量依赖性方式反转这些变化。这些研究结果表明,斯科尔蛋白可以缓解神经元线粒体功能障碍,并改善自闭症大鼠的神经症状。本研究经费/ IAEC,SIRSA,哈里亚纳州的批准于2014年3月3日批准(批准号/ IAEC / 2014/03 / 03)。

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