title: L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.
abstract: 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 rapamycin (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.
authors.affiliation: 1] Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan [2] Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Department of Cell Biology and Neuroscience, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shimura
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hira
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: 1] Department of Cell Biology and Neuroscience, Juntendo University School of Medicine, Tokyo, Japan [2] Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Urabe
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000473:pathology*; D002331:Carnitine / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D014803:Vitamin B Complex / Q000494:pharmacology; D066127:White Matter / Q000187:drug effects / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D014803:Vitamin B Complex; D002331:Carnitine