Gene expression effects of lithium and valproic acid in a serotonergic cell line

Balasubramanian, Diana; Pearson, John; Kennedy, Martin A.

doi:10.1152/physiolgenomics.00069.2018

Cited by 18 publications

(13 citation statements)

References 72 publications

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“…To relate our results to previous lithium findings, we compared the full set of DGE and DTE-only genes (n = 1108) with a set of genes associated with lithium in 18 previous transcriptomic reports [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] identified through a systematic literature search (Supplementary Materials and Methods). We found overlap with 112 genes (10.1%), many of them having similar direction and magnitude of effect (Table S3).…”

Section: Comparison Between Identified Genes and Previous Findingsmentioning

confidence: 99%

Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study

Akkouh

Skrede

Holmgren

et al. 2019

Neuropsychopharmacol.

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Lithium has been the first-line treatment for bipolar disorder (BD) for more than six decades. Although the molecular effects of lithium have been studied extensively and gene expression changes are generally believed to be involved, the specific mechanisms of action that mediate mood regulation are still not known. In this study, a multi-step approach was used to explore the transcriptional changes that may underlie lithium's therapeutic efficacy. First, we identified genes that are associated both with lithium exposure and with BD, and second, we performed differential expression analysis of these genes in brain tissue samples from BD patients (n = 42) and healthy controls (n = 42). To identify genes that are regulated by lithium exposure, we used highsensitivity RNA-sequencing of corpus callosum (CC) tissue samples from lithium-treated (n = 8) and non-treated (n = 9) rats. We found that lithium exposure significantly affected 1108 genes (FDR < 0.05), 702 up-regulated and 406 down-regulated. These genes were mostly enriched for molecular functions related to signal transduction, including well-established lithium-related pathways such as mTOR and Wnt signaling. To identify genes with differential expression in BD, we performed expression quantitative trait loci (eQTL) analysis on BD-associated genetic variants from the most recent genome-wide association study (GWAS) using three different gene expression databases. We found 307 unique eQTL genes regulated by BD-associated variants, of which 12 were also significantly modulated by lithium treatment in rats. Two of these showed differential expression in the CC of BD cases: RPS23 was significantly down-regulated (p = 0.0036, fc = 0.80), while GRIN2A showed suggestive evidence of down-regulation in BD (p = 0.056, fc = 0.65). Crucially, GRIN2A was also significantly up-regulated by lithium in the rat brains (p = 2.2e-5, fc = 1.6), which suggests that modulation of GRIN2A expression may be a part of the therapeutic effect of the drug. These results indicate that the recent upsurge in research on this central component of the glutamatergic system, as a target of novel therapeutic agents for affective disorders, is warranted and should be intensified.

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Section: Comparison Between Identified Genes and Previous Findingsmentioning

confidence: 99%

Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study

Akkouh

Skrede

Holmgren

et al. 2019

Neuropsychopharmacol.

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“…Therefore, the lithium we intake increases markedly daily. It is reported that several genes are significantly changing under this level [43]. But the level is much lower than the toxic concentration to humans.…”

Section: Discussionmentioning

confidence: 95%

The toxicity of lithium to human cardiomyocytes

Shen

Xiu-juan

et al. 2020

Environ Sci Eur

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Background: Lithium is widely used in the electronic consumer market and electric vehicles and has a great contribution to the world economy, resulting in large quantities of lithium waste in the environment. The Yangtze River Basin is one of the most developed areas in China. However, the environmental influence of lithium in the Yangtze River Basin and its roles in cardiomyocytes have not yet been clarified. Results: Here, we found that the concentration of lithium in the water environment is very high in Shanghai, as well as in tap water, which might be caused by the pollution of lithium batteries. Lithium inhibits cell viability and proliferation of human cardiomyocytes. Moreover, lithium promotes cell apoptosis significantly. And we found that lithium controls cardiomyocytes' functions through regulating glycogen synthase kinase 3 beta signaling. Conclusions: This study reveals that the water environment of Shanghai might be polluted by the lithium batteries; and the enrichment of lithium might cause damage to human cardiomyocytes. It is imperative to detect lithium concentration in the water environments (such as tap water and irrigation water) and effectively recycle lithium batteries in the future.

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“…Therefore the lithium we intake increases markedly daily. It is reported that several genes are significantly changing under this level [45]. But the level is much lower than the toxic concentration to humans.…”

Section: Discussionmentioning

confidence: 95%

The toxicity of lithium to human cardiomyocytes

Shen

Shi

et al. 2020

Preprint

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Background: Lithium is widely used in the electronic consumer market and electric vehicles and has a great contribution in the world economy, resulting in large quantities of lithium waste in the environment. Yangtze River basin is one of the most developed areas in China. However, the environment influence of lithium in the Yangtze River basin and its roles in cardiomyocytes has not yet been clarified. Results: Here we found that the concentration of lithium in the water environment is very high in Shanghai, as well as in tap water, which might be cause by the pollution of lithium batteries. Lithium inhibits not only cell viability of human cardiomyocytes, but also cell proliferation. Moreover, lithium promotes cell apoptosis of cardiomyocytes significantly. And we found that lithium controls cardiomyocytes' functions through regulating Gsk3β signaling. Conclusions: This study reveals that the water environment of Shanghai might be polluted by the lithium batteries; and the enrichment of lithium may cause damage to human cardiomyocytes; and it is imperative to detect lithium concentration in the water environments (such as tap water and irrigation water) and effectively recycle lithium batteries in the future.

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Gene expression effects of lithium and valproic acid in a serotonergic cell line

Cited by 18 publications

References 72 publications

Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study

Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study

The toxicity of lithium to human cardiomyocytes

The toxicity of lithium to human cardiomyocytes

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