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Axonal Regeneration and Tissue Repair

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

L-carnitine enhances axonal plasticity and improves white matter lesions after chronic hypoperfusion in rat brain

  • P3-080
  • 上野 祐司 / Yuji Ueno:1 小池 正人 / Masato Koike:3 島田 佳明 / Yoshiaki Shimada:1 志村 秀樹 / Hideki Shimura:2 内山 安男 / Yasuo Uchiyama:3 服部 信孝 / Nobutaka Hattori:1 卜部 貴夫 / Takao Urabe:2 
  • 1:順天堂大学神経学講座 / Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan 2:順天堂大学医学部附属浦安病院神経学講座 / Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan 3:順天堂大学神経生物学・形態学講座 / Department of Cell Biology and Neuroscience, Juntendo University School of Medicine, Tokyo, Japan 

Chronic cerebral hypoperfusion causes white matter lesions with oxidative stress and cognitive impairment. However, the biological mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated.Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries were treated with or without L-carnitine. Immunohistochemical and western blot analyses, and behavioural tests were performed after ligation of the bilateral common carotid arteries. L-carnitine-treated rats exhibited significantly reduced escape latency at 28 days after operation in the Morris water maze task. L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with reduction of phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increases of phosphorylated Akt and mammalian target of rapamycin (mTOR), as well as reduction of semaphorin 3A at 28 days after chronic hypoperfusion. Axonal phosphorylated Akt and mTOR protein were present in pNFH+ axons at 28 days in the L-carnitine-treated rats. In contrast, axons at 28 days in the vehicle-treated rats exhibited many fewer axonal phosphorylated Akt and mTOR proteins. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. Collectively, these findings demonstrate that L-carnitine regulates the PTEN/Akt/mTOR signalling pathway and semaphorin 3A, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving white matter lesions and cognitive impairment in a rat chronic hypoperfusion model.

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