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Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

  • Kim, Yonghoon (Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University) ;
  • Kim, Jeongtae (Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University) ;
  • Ahn, Meejung (Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University) ;
  • Shin, Taekyun (Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University)
  • 투고 : 2017.05.24
  • 심사 : 2017.07.24
  • 발행 : 2017.09.30

초록

Glycogen synthase kinase $(GSK)-3{\beta}$ and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of $GSK-3{\beta}$, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative $GSK-3{\beta}$-associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of $GSK-3{\beta}$ (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that $GSK-3{\beta}$ becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of $GSK-3{\beta}$ and the associated molecules Nrf-2 and HO-1.

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과제정보

연구 과제 주관 기관 : National Research Foundation of Korea (NRF)

피인용 문헌

  1. The effect of lithium chloride on BDNF, NT3, and their receptor mRNA levels in the spinal contusion rat models vol.41, pp.6, 2017, https://doi.org/10.1080/01616412.2019.1588507
  2. A Pivotal Role of the Nrf2 Signaling Pathway in Spinal Cord Injury: A Prospective Therapeutics Study vol.19, pp.3, 2017, https://doi.org/10.2174/1871527319666200604175118