Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1.
10.5115/acb.2017.50.3.207
- Author:
Yonghoon KIM
1
;
Jeongtae KIM
;
Meejung AHN
;
Taekyun SHIN
Author Information
1. Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju, Korea. shint@jejunu.ac.kr, healthy@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Spinal cord injuries;
Lithium;
Glycogen synthase kinase-3β;
NF-E2-related factor-2;
Heme oxygenase-1
- MeSH:
Animals;
Blotting, Western;
Glycogen Synthase Kinases;
Glycogen Synthase*;
Glycogen*;
Heme Oxygenase-1*;
Heme*;
Hemorrhage;
Lithium Chloride;
Lithium*;
Phosphorylation;
Rats*;
Spinal Cord Injuries*;
Spinal Cord*
- From:Anatomy & Cell Biology
2017;50(3):207-213
- CountryRepublic of Korea
- Language:English
-
Abstract:
Glycogen synthase kinase (GSK)-3β 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-3β, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative GSK-3β–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-3β (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-3β becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of GSK-3β and the associated molecules Nrf-2 and HO-1.
