L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain
L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain
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DOI：
10.1038/jcbfm.2014.210
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发表时间：
2015-03-01
影响因子：
6.3
通讯作者：
Urabe, Takao
中科院分区：
文献类型：
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作者：
Ueno, Yuji;Koike, Masato;Urabe, Takao
慢性脑灌注不足导致白质病变（WML），伴有氧化应激和认知障碍。然而，慢性脑灌注不足下调节轴突可塑性的生物学机制尚未得到充分研究。在这里，我们研究是否L-肉碱，抗氧化剂，增强轴突可塑性和少突胶质细胞的表达，并探讨了在大鼠慢性低灌注模型中介导轴突可塑性的信号通路。结扎双侧颈总动脉（LBCCA）的成年雄性Wistar大鼠用或不用L-肉碱治疗。在慢性低灌注后28天，左旋卡尼汀治疗的大鼠在Morris水迷宫任务中表现出显著减少的逃避潜伏期。Western blot分析表明，在慢性低灌注后28天，L-肉毒碱增加磷酸化高分子量神经丝（pNFH）的水平，同时减少10号染色体上缺失的磷酸化磷酸酶张力蛋白同源物（PTEN），并增加磷酸化Akt和哺乳动物雷潘霉素靶蛋白（mTOR）。左旋卡尼汀减少脂质过氧化和氧化DNA损伤，并增强少突胶质细胞标记物的表达和髓鞘厚度慢性低灌注后。L-肉毒碱调节PTEN/Akt/mTOR信号通路，并增强轴突可塑性，同时改善氧化应激和增加轴突的少突胶质细胞髓鞘形成，从而改善大鼠慢性低灌注模型中的WML和认知障碍。
Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent With a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapannycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.