Deciphering the lithium transcriptome: Microarray profiling of lithium-modulated gene expression in human neuronal cells

Seelan, Ratnam S.; Khalyfa, Abdelnaby; Lakshmanan, Jaganathan; Casanova, Manuel F.; Parthasarathy, R.

doi:10.1016/j.neuroscience.2007.10.045

Cited by 72 publications

(57 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a more recent microarray study by McQuillin et al (2007) over 10 genes related to the phosphatidylinositol (PI) signaling system were shown to be affected by chronic lithium treatment in mouse brain. Changes in PI cycle-related genes were also reported in two additional microarray studies assessing Li's action (Bosetti et al, 2002;Seelan et al, 2008).…”

Section: Introductionmentioning

confidence: 65%

Inositol-Related Gene Knockouts Mimic Lithium’s Effect on Mitochondrial Function

Toker

Bersudsky

Plaschkes

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

The inositol-depletion hypothesis proposes that lithium attenuates phosphatidylinositol signaling. Knockout (KO) mice of two genes (IMPA1 or Slc5a3), each encoding for a protein related to inositol metabolism, were studied in comparison with lithiumtreated mice. Since we previously demonstrated that these KO mice exhibit a lithium-like neurochemical and behavioral phenotype, here we searched for pathways that may mediate lithium's/the KO effects. We performed a DNA-microarray study searching for pathways affected both by chronic lithium treatment and by the KO of each of the genes. The data were analyzed using three different bioinformatics approaches. We found upregulation of mitochondria-related genes in frontal cortex of lithium-treated, IMPA1 and Slc5a3 KO mice. Three out of seven genes differentially expressed in all three models, Cox5a, Ndufs7, and Ndufab, all members of the mitochondrial electron transfer chain, have previously been associated with bipolar disorder and/or lithium treatment. Upregulation of the expression of these genes was verified by real-time PCR. To further support the link between mitochondrial function and lithium's effect on behavior, we determined the capacity of chronic low-dose rotenone, a mitochondrial respiratory chain complex I inhibitor, to alter lithium-induced behavior as measured by the forced-swim and the amphetamine-induced hyperlocomotion paradigms. Rontenone treatment counteracted lithium's effect on behavior, supporting the proposition suggested by the bioinformatics analysis for a mitochondrial function involvement in behavioral effects of lithium mediated by inositol metabolism alterations.The results provide support for the notion that mitochondrial dysfunction is linked to bipolar disorder and can be ameliorated by lithium. The phenotypic similarities between lithium-treated wild-type mice and the two KO models suggest that lithium may affect behavior by altering inositol metabolism.

show abstract

Section: Introductionmentioning

confidence: 65%

Inositol-Related Gene Knockouts Mimic Lithium’s Effect on Mitochondrial Function

Toker

Bersudsky

Plaschkes

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Another pathway involved in uPA expression is PI3 kinase (PI3 K) pathway, converting to Wnt signaling on the point of GSK-3 complex (Seelan et al 2008). As we observed inhibition of basal uPA activity after treatment with LiCl, GSK-3 inhibitor, we explored GSK-3 a/b activity under experimental conditions.…”

Section: Resultsmentioning

confidence: 99%

Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition

et al. 2014

View full text Add to dashboard Cite

The urokinase plasminogen activator (uPA) system is a complex regulator of extracellular proteolysis which is involved in various physiological and pathological processes. The major components of this system are the serine protease uPA, two inhibitors PAI-1 and PAI-2, and the receptor uPAR. It has been previously shown by several groups that the uPA system has an important role in cancer progression and therefore its possible prognostic and therapeutic value has been evaluated. The aim of this study is to tackle the role of poly(ADP-ribosyl)ation in the induction of uPA activity in a glioblastoma cell line, A1235. This cell line is sensitive to alkylation damage and is a model for drug treatment. The components of the uPA system and the level of DNA damage were analyzed after alkylation agent treatment in combination with poly(ADP-ribose)polymerase-1 (PARP-1) inhibition. Here we show that the increase in uPA activity results from the net balance change between uPA and its inhibitor at mRNA level. Further, PARP-1 inhibition exerts its influence on uPA activity through DNA damage increase. Involvement of several signaling pathways, as well as cell specific regulation influencing the uPA system are discussed.

show abstract

“…It has been hypothesized that the effects of the chronic lithium treatment are due to its ability to alter the balance between neurotransmitter and neuropeptide signaling pathways [13]. Moreover, chronic lithium treatment seems to regulate gene expression in the brain [14], and an investigation of lithium effects over the transcriptome of a human neuronal cell culture indicated the up-regulation of neuroprotective genes together with the downregulation of genes encoding pro-apoptotic proteins [15]. The lithium treatment of neurons derived from bipolar disease patients altered the uptake and the intracellular levels of calcium and redirected neural stem cell fate [16].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

“…Quality and quantity of RNA samples were determined using NanoDrop ® (ND-1000-Thermo Fisher Scientific, Inc-USA) and the integrity of the total RNA was checked by electrophoresis in 1 % agarose gels containing 1 M of guanidine isothiocyanate. cDNA synthesis was performed at 42 °C for 90 min, using 1 μg of total RNA, 200U of ImProm-II™ Reverse Transcriptase (Promega, Madison, WI, USA), 0.5 μg oligo (dT) [12][13][14][15][16][17][18] , 0.5 mM dNTPs, 3 mM MgCl 2 and 1 × reaction buffer in a 20 μl reaction volume.…”

Section: Rna Extraction and Cdna Synthesismentioning

confidence: 99%

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Mury

Silva

Barbosa

et al. 2015

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

show abstract

Deciphering the lithium transcriptome: Microarray profiling of lithium-modulated gene expression in human neuronal cells

Cited by 72 publications

References 75 publications

Inositol-Related Gene Knockouts Mimic Lithium’s Effect on Mitochondrial Function

Inositol-Related Gene Knockouts Mimic Lithium’s Effect on Mitochondrial Function

Modulation of urokinase plasminogen activator system by poly(ADP-ribose)polymerase-1 inhibition

Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Contact Info

Product

Resources

About