Glatiramer acetate could be a potential antidepressant through its neuroprotective and anti-inflammatory effects

Abstract

Antidepressants that act by increasing the activity of central serotonergic or noradrenergic systems are the main biological treatments for major depressive disorder (MDD). Although these agents are generally safe and effective, they are far from ideal due to their slow onset and a substantial proportion of MDD patients do not clinically improve, despite maximal dosing. Thus, the development of new antidepressants based on novel theories may help to develop faster and more effective antidepressant agents. Over the last decade, there has been an impressive accumulation of data about non-monoamine systems that might mediate the pathogenesis of, and therapeutic mechanisms in, MDD. For example, MDD has been associated with a decreased central brain-derived neurotrophic factor (BDNF) state and activating the BDNF-signaling pathway may play an important role in the mechanisms of antidepressant therapeutic action. Glatiramer acetate (GA) is a collection of synthetic polypeptides indicated as therapy for relapsing-remitting multiple sclerosis. Both preclinical and clinical studies have demonstrated that peripheral GA administration can enhance central BDNF activity or increase serum BDNF levels. Furthermore, MDD has been associated with an inflammatory process in the brain. Animal studies have demonstrated that GA administration has a central anti-inflammatory effect through the release of interleukin-10. Finally, recent animal studies have suggested that psychosocial stress reduces neurogenesis, whereas antidepressant treatment increases neurogenesis and blocks the effects of stress. Peripheral administration of GA was found to augment neurogenesis, including cell proliferation, migration, and differentiation in rodent brain. From the above evidence, GA could have antidepressant effects by increasing central BDNF, stimulating neurogenesis or through its anti-inflammatory effect. It is also suggested that immediate GA treatment after stress may prevent the development of stress-related psychiatric disorders such as MDD and post-traumatic stress disorder.