title: Targeting astrocytes in bipolar disorder.
abstract: Astrocytes are homeostatic cells of the central nervous system, which are critical for development and maintenance of synaptic transmission and hence of synaptically connected neuronal ensembles. Astrocytic densities are reduced in bipolar disorder, and therefore deficient astroglial function may contribute to overall disbalance in neurotransmission and to pathological evolution. Classical anti-bipolar drugs (lithium salts, valproic acid and carbamazepine) affect expression of astroglial genes and modify astroglial signalling and homeostatic cascades. Many effects of both antidepressant and anti-bipolar drugs are exerted through regulation of glutamate homeostasis and glutamatergic transmission, through K(+) buffering, through regulation of calcium-dependent phospholipase A2 (that controls metabolism of arachidonic acid) or through Ca(2+) homeostatic and signalling pathways. Sometimes anti-depressant and anti-bipolar drugs exert opposite effects, and some effects on gene expression in drug treated animals are opposite in neurones vs. astrocytes. Changes in the intracellular pH induced by anti-bipolar drugs affect uptake of myo-inositol and thereby signalling via inositoltrisphosphate (InsP3), this being in accord with one of the main theories of mechanism of action for these drugs.
authors.affiliation: a Laboratory of Metabolic Brain Diseases, Institute of Metabolic Disease Research and Drug Development , China Medical University , Shenyang , P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: a Laboratory of Metabolic Brain Diseases, Institute of Metabolic Disease Research and Drug Development , China Medical University , Shenyang , P. R. China.
authors.forename: Baoman
authors.initials: B
authors.lastname: Li
authors.affiliation: b Faculty of Life Science , The University of Manchester , Manchester , UK.|c Achucarro Center for Neuroscience, IKERBASQUE , Basque Foundation for Science , Bilbao , Spain.|d Department of Neurosciences , University of the Basque Country UPV/EHU and CIBERNED , Leioa , Spain.|e University of Nizhny Novgorod , Nizhny Novgorod , Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000473:pathology*; D002220:Carbamazepine / Q000627:therapeutic use; D006801:Humans; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D002220:Carbamazepine; D014635:Valproic Acid
keywords: Astrocytes; bipolar disorder; mechanism of drug action