Title:Effects of GABAergic Agents on Multiple Sclerosis. A Narrative Review of In-vivo Models
Volume: 22
Issue: 10
Author(s): Еleni Stamoula, Alexandra Ainatzoglou, Ioannis Dardalas, Theofanis Vavilis, Vasileios-Periklis Stamatellos, Spyridon Siafis, Thomas Psathas, Ioanna Boskou and Georgios Papazisis*
Affiliation:
- Department of Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Clinical Trials Unit, Special Unit for Biomedical
Research and Education, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Keywords:
GABA, GABAergic, MS, EAE, CNS, immunomodulatory, neuroinflammation.
Abstract:
Background: Multiple sclerosis (MS) is a lifelong deteriorating disease characterized by
multiple heterogeneous symptoms. Being an autoimmune disease of the central nervous system, mainly
affecting the myelin sheath of the nerves ordinarily results in neurological symptoms. GABA has
numerous effects on the immune cells, altering cytokine production, cell migration and proliferation.
Immune cells express GABA receptors making GABA an inflammation modulator. Therefore, GABAergic-
associated agents could provide a compatible add-on therapy for MS patients alleviating their
symptoms and providing better quality years.
Objective: This review aims to highlight and provide evidence of the potential benefits of a secondary
treatment option in MS patients, aiming to better manage this disease.
Methods: We conducted a literature search through PubMed, Scopus and Google Scholar for GABA
agonists, antagonists and modulators used in the in vivo model of experimental autoimmune encephalomyelitis
(EAE), taking into consideration certain inclusion and exclusion criteria.
Results: In vivo studies for GABA-a and GABA-b agonists and modulators showed regulation of the
autoimmune response in EAE mice. Increased preservation of myelinated sensitive fibers and diminished
axonal damage in the CNS was also demonstrated. Further, decreased mononuclear inflammatory
infiltration, pro-inflammatory cytokines reduction and reduced levels of Reactive oxygen species
(ROS) were also reported. Biological results included decreased peak disease severity, duration, clinical
scores and EAE incidence in the treatment groups.
Conclusion: GABA agonists and modulators efficiently challenged different aspects of disease pathophysiology
in vivo models of EAE. The studies showed a significant relevance of neuroprotection via
modulation of the autoimmune response in EAE rats, indicating that they should be considered proper
therapeutic candidates for clinical use, while also further clinical studies could empower their administration
in clinical practice.
