Journal
EXPERT REVIEW OF NEUROTHERAPEUTICS
Volume 16, Issue 6, Pages 649-657Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/14737175.2016.1171144
Keywords
Astrocytes; bipolar disorder; mechanism of drug action
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Funding
- National Natural Science Foundation of China [31171036]
- Ministry of Education and Science of the Russian Federation [02.B.49.21.0003]
- Lobachevsky State University of Nizhny Novgorod [02.B.49.21.0003]
- Russian Scientific Foundation [14-15-00633]
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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 antibipolar 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 A(2) (that controls metabolism of arachidonic acid) or through Ca2+ 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 (InsP(3)), this being in accord with one of the main theories of mechanism of action for these drugs.
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