ReviewNeurochemical research2012
Chronic treatment with anti-bipolar drugs causes intracellular alkalinization in astrocytes, altering their functions.
Review in Neurochemical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Valproic Acid Promotes the Differentiation of Satellite Glial Cells into Neurons via the pH-Dependent Pathway.Biomolecules · 2025Article
- Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.Biomedicines · 2024Review
- Astrocyte Cultures Mimicking Brain Astrocytes in Gene Expression, Signaling, Metabolism and KNeurochemical research · 2017Article
- Glial pathology in bipolar disorder: potential therapeutic implications.CNS neuroscience & therapeutics · 2015Review
- Fluoxetine induces alkalinization of astroglial cytosol through stimulation of sodium-hydrogen exchanger 1: dissection of intracellular signaling pathways.Frontiers in cellular neuroscience · 2015Article
- Role of glycogenolysis in stimulation of ATP release from cultured mouse astrocytes by transmitters and high K+ concentrations.ASN neuro · 2014Article
- Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines) Ameliorating Mood Disorders.Journal of signal transduction · 2014Review
- Methodological limitations in determining astrocytic gene expression.Frontiers in endocrinology · 2013Review
- Comparison between drug-induced and K⁺-induced changes in molar acid extrusion fluxes (JH⁺) and in energy consumption rates in astrocytes.Neurochemical research · 2013Article
- Cell-specific mRNA alterations in Na+, K+-ATPase α and β isoforms and FXYD in mice treated chronically with carbamazepine, an anti-bipolar drug.Neurochemical research · 2013Article
- Requirement of glycogenolysis for uptake of increased extracellular K+ in astrocytes: potential implications for K+ homeostasis and glycogen usage in brain.Neurochemical research · 2013Article
- Astrocytic and neuronal accumulation of elevated extracellular K(+) with a 2/3 K(+)/Na(+) flux ratio-consequences for energy metabolism, osmolarity and higher brain function.Frontiers in computational neuroscience · 2013Article
- The Glutamate-Glutamine (GABA) Cycle: Importance of Late Postnatal Development and Potential Reciprocal Interactions between Biosynthesis and Degradation.Frontiers in endocrinology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bipolar disorder I and II are affective disorders with mood changes between depressive and manic (bipolar I) or hypomanic (bipolar II) periods. Current therapy of these conditions is chronic treatment with one or more of the anti-bipolar drugs, Li(+) ('lithium'), carbamazepine and valproic acid. The pathophysiology of bipolar disorder is multifactorial and far from clear. Recent data on the dependence of normal brain function on neuronal-astrocytic interactions raise the possibility of astrocytic involvement. We will discuss our previously published and new results on effects of chronic treatment of primary cultures of normal mouse astrocytes with any of three conventional anti-bipolar drugs. The focus will be on several drug-induced events in relation to therapeutic effects of the drugs, such as myo-inositol uptake, intracellular pH and alkalinization, drug-induced modulation of glutamatergic activity in astrocytes and release of astrocytic 'gliotransmitters'. Finally, we will discuss the importance of phospholipase A2 (PLA(2)) and arachidonic acid cascade in drug-treated astrocytes, partly based on Dr. Barneda Cuirana's published thesis. All three drugs cause gradual intracellular alkalinization through different mechanisms. Alkalinization inhibit myo-inositol uptake, resulting in reduced inositolphosphate/phospholipid signaling. Accordingly, transmitter-induced increase in free intracellular Ca(2+) ([Ca(2+)](i)) becomes inhibited, aborting release of astrocytic 'gliotransmitters'. The reduction of "gliotransmitter" effects on neurons may have therapeutic effects in mania. Alkalinization also up-regulates expression of cPLA(2), an enzyme releasing arachidonic acid, and triggered arachidonic acid cascade and production, but perhaps not release, of prostaglandins. Whenever tested, identical effects were observed in freshly isolated astrocytes, but not neurons, from carbamazepine-treated healthy animals.
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