Lithium prevents and ameliorates experimental autoimmune encephalomyelitis

Area of Science:

• Neuroimmunology
• Pharmacology

Background:

• Experimental autoimmune encephalomyelitis (EAE) in animals shares characteristics with multiple sclerosis (MS), a disease lacking adequate therapies.
• Glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in neuroinflammatory conditions.

Purpose of the Study:

• To investigate the therapeutic potential of lithium, a GSK3 inhibitor, in ameliorating EAE in mice.
• To explore the role of GSK3 activity in EAE pathogenesis.

Main Methods:

• Mice were immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or proteolipid protein peptide139-151 to induce EAE.
• Lithium was administered either as a pretreatment or post-onset of the disease.
• Disease severity, demyelination, immune cell infiltration, and T cell responses were assessed.
• Mice with constitutively active GSK3 were used to confirm GSK3's role.

Main Results:

• Lithium pretreatment significantly suppressed EAE clinical symptoms, reduced demyelination, microglia activation, and leukocyte infiltration.
• Post-onset lithium administration improved disease severity and facilitated partial recovery.
• Mice with active GSK3 showed exacerbated EAE.
• Lithium suppressed MOG35-55-reactive T cell differentiation and pro-inflammatory cytokine production (IFN-gamma, IL-6, IL-17).
• In relapsing/remitting EAE, lithium provided long-term protection, with rapid relapse upon withdrawal.

Conclusions:

• Lithium effectively suppresses EAE, indicating GSK3 is a viable therapeutic target for multiple sclerosis.
• Inhibition of GSK3 by lithium may offer a novel therapeutic approach for CNS autoimmune and inflammatory diseases.