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S005-4

Modulating Neuro-Inflammation as a Novel Target for Antidepressant Drug
Development

Feyza Aricioglu

Marmara University, Department of Pharmacology and Psychopharmacology Research Unit, Istanbul-Turkey

Content: Rapidly accumulating evidence suggests that the glutamatergic system plays an important
role in the neuropathology and treatment of major depressive disorder (MDD). Recently it has been
shown that ketamine has a rapid and long lasting antidepressant activity after a single dose. Basic
researchers demonstrated that ketamine rapidly activates the so called “mammalian target of
rapamycin” (mTOR) pathway, one of many such pathways that perform signal transduction in
neurons. This new approach may be a revolutionary break-through in the treatment of depression and
it might lead to novel therapeutic targets for antidepressant drug development. Today a growing body
of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3
(GSK-3) in MDD. GSK-3 is widely expressed in many tissues with the highest levels in the brain
and is regulated by neuromodulators such as brain-derived neurotrophic factor, responsible for
phosphorylating GSK-3. It has been suggested that there is a link between inflammatory processes
and depression. High plasma levels of pro-inflammatory cytokines such as IL-1β,
IL-6 and TNF-α have been reported by several clinical studies in patients with
depression. In addition, plasma levels of these pro-inflammatory cytokines are shown to be
decreased with antidepressant therapies. Thus, great effort has been made to discover novel
therapeutic implications targeting immune mechanisms that would replace currently available drugs.