How does lithium mediate its therapeutic effects?

Patočka, Jiří; Šárek, Milan

doi:10.32725/jab.2005.003

Cited by 5 publications

(4 citation statements)

References 87 publications

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“…Myo-inositol is the product of inositol monophosphate hydroxyldephosphorylation by inositol monophosphatase (IMP). It is stored in glial cells, but is trafficked to neurons, where it becomes a precursor of phosphatidylinositol-4,5-biphosphate (PIP2) and participates in the PIP2 secondary messenger system (8,30). Therefore, it can be used as a marker of glial function or the extent of gliosis.…”

Section: Discussionmentioning

confidence: 99%

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Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression

et al. 2014

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Section: Discussionmentioning

confidence: 99%

“…MDD is a risk factor for migraine progression. Both migraine and depression decrease health-related quality of life; therefore, treatment of migraine patients with MDD is challenging (1,30). One helpful treatment for migraine patients with MDD might be rTMS over the DLPFC; however, further studies are needed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression

et al. 2014

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“…Lithium is a gold standard therapeutic drug used in psychiatry for the treatment of manic depression since its establishment in 1949 [1,2]. It is an alkali metal and a monovalent trace element known to be reactive due to its unpaired electron which contributes to its chemical reactivity [3]. Lithium regulates several major biological processes which include receptor-mediated signalling, ion transport, hormonal and circadian systems, and inflammatory signalling pathways [3].…”

Section: Introductionmentioning

confidence: 99%

“…It is an alkali metal and a monovalent trace element known to be reactive due to its unpaired electron which contributes to its chemical reactivity [ 3 ]. Lithium regulates several major biological processes which include receptor-mediated signalling, ion transport, hormonal and circadian systems, and inflammatory signalling pathways [ 3 ]. Lithium exerts most of its effects on several bioprocesses through inhibition or activation of vital enzymes such as inhibition of inositol monophosphatase (IMPase), inositol polyphosphate 1-phosphatase (IPPase), bisphosphate 3-nucleotidase (BPNT1), fructose 1,6 bisphosphate (FBPase), nuclear factor-E2 factor 2 (Nrf 2), cyclooxygenase (COX), and GSK-3 β [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

Makola

Mbazima

Mokgotho

et al. 2020

International Journal of Inflammation

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Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration albeit unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-κB (NF-κB) activity and mRNA expression of multiple oxidative stress-related NF-κB genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H2DCFDA fluorescence intensity, indicative of reduced reactive oxygen species (ROS) production, was observed in LPS-activated Raw 264.7 macrophages treated with lithium. Lithium has been shown to lower the production of the chemokine RANTES; furthermore, this inhibitory action of lithium has been suggested to be independent of glycogen synthase kinase-3 β (GSK3β) activity. It is shown here that lithium modulates the expression of several inflammatory genes including IκB-α, TRAF3, Tollip, and NF-κB1/p50 which are regulators of the NF-κB pathway. Moreover, lithium inhibits NF-κB activity by lowering nuclear translocation of NF-κB in LPS-activated macrophages. This is the first study to associate Tollip, Traf-3, and IκB-α mRNA expression with lithium effect on NF-κB activity in LPS-activated Raw 264.7 macrophages. Although these effects were obtained using extratherapeutic concentrations of lithium, results of this study provide useful information towards understanding the mode of action of lithium. This study associates lithium with reduced oxidative stress in LPS-activated Raw 264.7 macrophages and further suggests candidate molecular targets for the regulation of oxidative stress-related diseases using lithium beyond bipolar disorders.

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Effect of lithium on the properties of a liquid crystal formed by sodium dodecylsulphate and decanol in aqueous solution

Bahamonde-Padilla

Espinoza

Weiss-López

et al. 2013

The Journal of Chemical Physics

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Understanding the molecular interactions that rule the physicochemical properties of molecular assemblies is of particular interest when trying to explain the behavior of much more complicated systems, such as the cell membranes. This work was devoted to study a discotic nematic lyotropic liquid crystal, formed by sodium dodecylsulphate (3% SDS-d25) and decanol (20% DeOH-α-d2), dissolved in aqueous solutions (0.1% D2O) of Na2SO4 or Li2SO4. The average size of the aggregates was estimated using fluorescence quenching experiments, and their dynamics were studied by measuring the (2)H-NMR quadrupole splitting (ΔνQ) and the longitudinal relaxation times (T1) of the deuterated species. To provide an atomic insight into these assemblies, molecular dynamics simulations of the systems were carried out with atomic detail. As a previous step in this study, a reparameterization of the standard GROMOS 87 force field was required to perform the equilibrated simulations and to prevent instabilities emerging during the simulations. Finally, an excellent agreement between simulation and experimental data was obtained. In addition, variations in the long range electrostatic interactions at the aggregate/solution interface, the orientation and the reorientational relaxation time of the water dipole, the translational diffusion coefficient of sodium ions, and the amphiphile-counterion coordination associated with the presence of Li(+) in the solution were other key aspects investigated to explain the variation in the quadrupole splittings (ΔνQ) in the presence of lithium in solution.

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How does lithium mediate its therapeutic effects?

Cited by 5 publications

References 87 publications

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression

The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

Effect of lithium on the properties of a liquid crystal formed by sodium dodecylsulphate and decanol in aqueous solution

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