Potential involvement of glycogen synthase kinase (GSK)-3β in a rat model of multiple sclerosis: evidenced by lithium treatment.
- Author:
Meejung AHN
1
;
Jeongtae KIM
;
Changnam PARK
;
Jinhee CHO
;
Youngheun JEE
;
Kyungsook JUNG
;
Changjong MOON
;
Taekyun SHIN
Author Information
- Publication Type:Original Article
- Keywords: Experimental autoimmune encephalomyelitis; GSK-3 signaling; Lithium; Rat model
- MeSH: Animals; Autoimmunity; Blotting, Western; Calcium; Central Nervous System; Central Nervous System Diseases; Encephalomyelitis, Autoimmune, Experimental; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases*; Glycogen Synthase*; Glycogen*; Humans; Interleukin-10; Lithium*; Models, Animal*; Multiple Sclerosis*; Paralysis; Phosphorylation; Rats*; Spinal Cord; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1
- From:Anatomy & Cell Biology 2017;50(1):48-59
- CountryRepublic of Korea
- Language:English
- Abstract: Glycogen synthase kinase (GSK)-3β has been known as a pro-inflammatory molecule in neuroinflammation. The involvement of GSK-3β remains unsolved in acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of this study was to evaluate a potential role of GSK-3β in central nervous system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment significantly delayed the onset of EAE paralysis and ameliorated its severity. Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis factor a but not that of interleukin 10. Western blot analysis showed that the phosphorylation of GSK-3β (p-GSK-3β) and its upstream factor Akt was significantly increased in the lithium-treated group. Immunohistochemical examination revealed that lithium treatment also suppressed the activation of ionized calcium binding protein-1-positive microglial cells and vascular cell adhesion molecule-1 expression in the spinal cords of lithium-treated EAE rats. These results demonstrate that lithium ameliorates clinical symptom of acute monophasic rat EAE, and GSK-3 is a target for the suppression of acute neuroinflammation as far as rat model of human CNS disease is involved.
