Major depressive disorders (MDD) a worldwide
psychiatric disease, is yet to be adequately controlled by
therapies; while the mechanisms of action of
antidepressants are yet to be fully characterised. In the last two decades, an increasing number of studies have demonstrated the role of astrocytes in the pathophysiology and
therapy of MDD.
Selective serotonin reuptake inhibitors (
SSRIs) are the most widely used
antidepressants. It is generally acknowledged that
SSRIs increase
serotonin levels in the central nervous system by inhibiting
serotonin transporters, although the
SSRIs action is not ideal. The
SSRIs antidepressant effect develops with considerable delay; their efficacy is low and frequent relapses are common. Neither cellular nor molecular pharmacological mechanisms of
SSRIs are fully characterised; in particular their action on astrocytes remain underappreciated. In this paper we overview potential therapeutic mechanisms of
SSRIs associated with astroglia and report the results of meta-analysis of studies dedicated to MDD,
SSRIs and astrocytes. In particular, we argue that
fluoxetine, the representative SSRI, improves depressive-like behaviours in animals treated with chronic mild stress and reverses depression-associated decrease in astrocytic
glial fibrillary acidic protein (GFAP) expression. In addition,
fluoxetine upregulates astrocytic
mRNA expression of 5-hydroxytriptamin/serotonin2B receptors (5-HT2BR). In summary, we infer that
SSRIs exert their anti-depressant effect by regulating several molecular and signalling pathways in astrocytes.