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Description
Major depressive disorder (MDD) is a leading cause of global disease burden, potentially lethal, due to the high risk of suicide. Current therapies of depression are not optimal, therapies are long-lasting and often ineffective. These shortcomings are mostly due to insufficient knowledge of molecular mechanisms of the disease. To improve the situation, several global initiatives exist to resolve biological basics of distinct symptoms of depression at the cellular and molecular level. These joined efforts provided evidence that glial cells, significantly contribute to pathophysiology of depression. In this project, we focus on one subtype of glia, namely astrocytes. These cells support neurons in several ways, e.g. they regulate levels of main excitatory neurotransmitter, glutamate, and they link this process to brain energy metabolism. Importantly, it has been reported that both, glutamate and energy homeostasis, are defective in the brain of patients suffering from depression, pointing to astrocytes as the possible cellular site of these disease. Strikingly, beneficial effects of recently developed antidepressant, ketamine, encompass restoration of glutamatergic synapse plasticity and normalization of glucose metabolism, suggesting that astrocytes may be a target of the drug. In this project, we aim to understand metabolic dysfunction of astrocytes in the context of depression to identify novel and more efficient therapeutic strategies.