Molecular Mechanisms of Action of Mood Stabilizers in Bipolar Disorder

2002 ◽  
pp. 112-136 ◽  
Author(s):  
D. van Calker
Keyword(s):  
Bipolar Disorder ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Mood Stabilizers

scholarly journals Bipolar disorder and mechanisms of action of mood stabilizers

2009 ◽  
Vol 61 (2) ◽  
pp. 185-209 ◽  
Author(s):  
Stanley I. Rapoport ◽  
Mireille Basselin ◽  
Hyung-Wook Kim ◽  
Jagadeesh S. Rao
Keyword(s):  
Bipolar Disorder ◽  
Mechanisms Of Action ◽  
Mood Stabilizers

Molecular targets of lithium action

2003 ◽  
Vol 15 (6) ◽  
pp. 316-340 ◽  
Author(s):  
B Corbella ◽  
E Vieta
Keyword(s):  
Bipolar Disorder ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Mood Stabilizers ◽  
Lithium Cation ◽  
Therapeutic Effects ◽  
Term Outcome ◽  
Long Term Outcome ◽  
The Brain

Lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. However, the precise mechanism of lithium action is not yet well understood. Extensive research aiming to elucidate the molecular mechanisms underlying the therapeutic effects of lithium has revealed several possible targets. The behavioral and physiological manifestations of the illness are complex and are mediated by a network of interconnected neurotransmitter pathways. Thus, lithium's ability to modulate the release of serotonin at presynaptic sites and modulate receptor-mediated supersensitivity in the brain remains a relevant line of investigation. However, it is at the molecular level that some of the most exciting advances in the understanding of the long-term therapeutic action of lithium will continue in the coming years. The lithium cation possesses the selective ability, at clinically relevant concentrations, to alter the PI second-messenger system, potentially altering the activity and dynamic regulation of receptors that are coupled to this intracellular response. Subtypes of muscarinic receptors in the limbic system may represent particularly sensitive targets in this regard. Likewise, preclinical data have shown that lithium regulates arachidonic acid and the protein kinase C signaling cascades. It also indirectly regulates a number of factors involved in cell survival pathways, including cAMP response element binding protein, brain-derived neurotrophic factor, bcl-2 and mitogen-activated protein kinases, and may thus bring about delayed long-term beneficial effects via under-appreciated neurotrophic effects. Identification of the molecular targets for lithium in the brain could lead to the elucidation of the pathophysiology of bipolar disorder and the discovery of a new generation of mood stabilizers, which in turn may lead to improvements in the long-term outcome of this devastating illness (1).

Dysregulation of ion fluxes in bipolar affective disorder

2000 ◽  
Vol 12 (3) ◽  
pp. 81-85 ◽  
Author(s):  
H.C.R. Grunze ◽  
J. Langosch ◽  
C. Normann ◽  
D. Rujescu ◽  
B. Amann ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Affective Disorder ◽  
Potassium Conductance ◽  
Mood Stabilizer ◽  
Mechanisms Of Action ◽  
Ion Fluxes ◽  
Mood Stabilizers ◽  
Calcium Antagonism ◽  
Sodium Calcium

ABSTRACTBipolar disorder has attracted numerous research from different neurobiological angles. This review will summarize selected findings focusing on the role of disturbed transmem-braneous ion fluxes. Several mood stabilizers exhibit a distinct profile including effects on sodium, calcium and potassium conductance. In summary, some decisive mechanisms of action as calcium antagonism and modulation of potassium currents may play a crucial role in the success of any given mood stabilizer in bipolar disorder.

scholarly journals Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

2020 ◽  
Author(s):  
Miki Bundo ◽  
Junko Ueda ◽  
Yutaka Nakachi ◽  
Kiyoto Kasai ◽  
Tadafumi Kato ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Mood Stabilizer ◽  
Cell Types ◽  
Mood Stabilizers ◽  
Differentially Methylated Region ◽  
Therapeutic Effects

AbstractBipolar disorder (BD) is a severe mental disorder characterized by repeated mood swings. Although genetic factors are collectively associated with the etiology of BD, the underlying molecular mechanisms, particularly how environmental factors affect the brain, remain largely unknown. We performed promoter-wide DNA methylation analysis of neuronal and nonneuronal nuclei in the prefrontal cortex of patients with BD (N=34) and controls (N=35). We found decreased DNA methylation at promoters in both cell types in the BD patients compared to the controls. Gene Ontology (GO) analysis of differentially methylated region (DMR)-associated genes revealed enrichment of molecular motor-related genes in neurons, chemokines in both cell types, and ion channel- and transporter-related genes in nonneurons. Detailed analysis further revealed that growth cone- and dendrite-related genes, including NTRK2 and GRIN1, were hypermethylated in neurons of BD patients. To assess the effect of medication, neuroblastoma cells were cultured under therapeutic concentrations of three different mood stabilizers (lithium, valproate, and carbamazepine). We observed that up to 37.9% of DMRs detected in BD overlapped with mood stabilizer-induced DMRs. Interestingly, mood stabilizer-induced DMRs showed the opposite direction of changes in DMRs in BD, suggesting the therapeutic effects of mood stabilizers on DNA methylation. Among the DMRs, 12 overlapped with loci identified by a previous genome-wide association study of BD. Finally, we performed qPCR analysis of 10 DNA methylation-related genes and found that DNMT3B was overexpressed in BD. The cell type-specific DMRs identified in this study will be useful for understanding the pathophysiology of BD.

scholarly journals Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder

2021 ◽  
Author(s):  
Miki Bundo ◽  
Junko Ueda ◽  
Yutaka Nakachi ◽  
Kiyoto Kasai ◽  
Tadafumi Kato ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Molecular Mechanisms ◽  
Mood Stabilizer ◽  
Cell Types ◽  
Mood Stabilizers ◽  
Therapeutic Effects ◽  
Go Analysis ◽  
A Genome

AbstractBipolar disorder (BD) is a severe mental disorder characterized by repeated mood swings. Although genetic factors are collectively associated with the etiology of BD, the underlying molecular mechanisms, particularly how environmental factors affect the brain, remain largely unknown. We performed promoter-wide DNA methylation analysis of neuronal and nonneuronal nuclei in the prefrontal cortex of patients with BD (N = 34) and controls (N = 35). We found decreased DNA methylation at promoters in both cell types in the BD patients. Gene Ontology (GO) analysis of differentially methylated region (DMR)-associated genes revealed enrichment of molecular motor-related genes in neurons, chemokines in both cell types, and ion channel- and transporter-related genes in nonneurons. Detailed GO analysis further revealed that growth cone- and dendrite-related genes, including NTRK2 and GRIN1, were hypermethylated in neurons of BD patients. To assess the effect of medication, neuroblastoma cells were cultured under therapeutic concentrations of three mood stabilizers. We observed that up to 37.9% of DMRs detected in BD overlapped with mood stabilizer-induced DMRs. Interestingly, mood stabilizer-induced DMRs showed the opposite direction of changes in DMRs, suggesting the therapeutic effects of mood stabilizers. Among the DMRs, 12 overlapped with loci identified in a genome-wide association study (GWAS) of BD. We also found significant enrichment of neuronal DMRs in the loci reported in another GWAS of BD. Finally, we performed qPCR of DNA methylation-related genes and found that DNMT3B was overexpressed in BD. The cell-type-specific DMRs identified in this study will be useful for understanding the pathophysiology of BD.

Mood Stabilizers, Oxidative Stress and Antioxidative Defense in Euthymia of Bipolar Disorder

2016 ◽  
Vol 15 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Susanne A. Bengesser ◽  
Nina Lackner ◽  
Armin Birner ◽  
Martina Platzer ◽  
Frederike T. Fellendorf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bipolar Disorder ◽  
Mood Stabilizers ◽  
Antioxidative Defense

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Gene Transcription as a Therapeutic Target in Leukemia

2021 ◽  
Vol 22 (14) ◽  
pp. 7340
Author(s):  
Alvina I. Khamidullina ◽  
Ekaterina A. Varlamova ◽  
Nour Alhuda Hammoud ◽  
Margarita A. Yastrebova ◽  
Alexandra V. Bruter
Keyword(s):  
Gene Transcription ◽  
Molecular Mechanisms ◽  
Hematological Malignancies ◽  
Mechanisms Of Action ◽  
Special Program ◽  
Cell Plasticity ◽  
Hematopoietic Stem ◽  
Promising Strategy ◽  
Tumor Cell Plasticity ◽  
Transcriptional Landscape

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.

Sign in / Sign up

Export Citation Format

Share Document