Lithium alleviates paralysis in experimental autoimmune neuritis in Lewis rats by modulating glycogen synthase kinase-3β activity

Importance: Guillain-Barr & eacute; syndrome (GBS)-like neuropathy mimics the leading cause of sporadic acute nontraumatic limb paralysis in individuals from developed countries. Experimental autoimmune neuritis (EAN) is an animal model of GBS and of syndromes such as acute canine polyradiculoneuritis, seen in dogs and cats. Objective: The involvement of glycogen synthase kinase (GSK)-3 beta, a pro-inflammatory molecule, in rat EAN is not fully understood. This study evaluated the potential role of GSK-3 beta in EAN through its inhibition by lithium. Methods: Lewis rats were injected with SP26 antigen to induce EAN. Lithium was administered from 1 day before immunization to day 14 post-immunization (PI). Then the rats were euthanized and their neural tissues were prepared for histological and Western blotting analyses. Results: Lithium, an inhibitor of GSK-3, significantly ameliorated EAN paralysis in rats, when administered from day 1 to day 14 PI. This corresponded with reduced inflammation in the sciatic nerves of EAN rats, where phosphorylation of GSK-3 beta was also upregulated, indicating suppression of GSK-3. Conclusions and relevance: These findings suggest that lithium, an inhibitor of GSK-3 beta, plays a significant role in ameliorating rat EAN paralysis, by suppressing GSK-3 beta and its related signals in EAN-affected sciatic nerves.