Neurobiological aspects of depressive disorder and antidepressant treatment: role of glia.
Depression is a complex disorder related to chronic inflammatory processes, chronic stress changes and a hippocampal response. There is a increasing knowledge about the role of glial cells in nutrient supply to neurons, maintenance of synaptic contacts and tissue homeostasis within the CNS. Glial cells, viewed in the past as passive elements with a limited influence on neuronal function, are becoming recognized as active partners of neurons and are starting to be discussed as a possible therapeutic target. Their role in the pathogenesis of depressive disorders is also being reconsidered. Attention is devoted to studies of the different types of antidepressants and their effects on transmembrane signaling, including levels of alpha subunits of G proteins in C6 glioma cells in vitro as a model of postsynaptic changes in vivo. These models indicate similarities in antidepressant effects on G proteins of brain cells and effector cells of natural immunity, natural killers and granulocytes. Thus, an antidepressant response can exhibit certain common characteristics in functionally different systems which also participate in disease pathogenesis. There are, however, differences in the astrocyte G-protein responses to antidepressant treatment, indicating that antidepressants differ in their effect on glial signalization. Today mainstream approach to neurobiological basis of depressive disorders and other mood illnesses is linked to abnormalities in transmembrane signal transduction via G-protein coupled receptors. Intracellular signalization cascade modulation results in the activation of transcription factors with subsequent increased production of a wide array of products including growth factors and to changes in cellular activity and reactivity.
Páv
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Clinic of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic. pavm@post.cz
Kovářů
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Fišerová
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Havrdová
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D000223:Adaptation, Psychological / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents