Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on β-catenin in mouse hippocampus

Kaidanovich-Beilin, Oksana; Milman, Anat; Weizman, Abraham; Pick, Chaim G.; Eldar-Finkelman, Hagit

doi:10.1016/j.biopsych.2004.01.008

Cited by 260 publications

(192 citation statements)

References 45 publications

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“…17 The major finding of this study is that three of the four GSK3B SNPs investigated are strongly associated with 4-week SSRI antidepressant therapeutic response. This association between the GSK3B genetic variants and therapeutic response to SSRIs is supported by data from animal studies showing that GSK3 inhibitors had antidepressant-like activity 10,11 and that fluoxetine inhibited GSK3B activity. 3 Furthermore, a recent study of Italian bipolar depression patients found that the C/C homozygote for the GSK3B rs334558 polymorphism (À50C/T) SNP showed acute effects of total sleep deprivation treatment on perceived mood.…”

Section: Discussionmentioning

confidence: 76%

“…9 Thirdly, two studies in 2004 demonstrated that rats treated with GSK3 inhibitors showed reduced duration of immobility when exposed to the forced swim test, a well-established model for antidepressant efficacy, suggesting the potential of GSK3 inhibitors as antidepressants. 10,11 Finally, a recent post-mortem study demonstrated that there was no change in GSK3B protein levels in the ventral prefrontal cortex of MDD patients but that GSK3B activity increased significantly compared with control subjects. 12 The human GSK3B, located on chromosome 3q13.33, is about 268 kb in length and includes 12 exons.…”

Section: Introductionmentioning

confidence: 99%

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Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

et al. 2008

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Evidence suggests that glycogen synthase kinase-3b (GSK3B) activity is increased significantly in the brain of patients with major depressive disorders (MDD). Inhibition of GSK3B is thought to be a key feature in the therapeutic mechanism of antidepressants. To investigate whether common genetic variants in the GSK3B gene are associated with MDD and the therapeutic response to antidepressants, four polymorphisms (rs334558 (À50 T4C), rs13321783 (IVS7 þ 9227 A4G), rs2319398 (IVS7 þ 11660 G4T) and rs6808874 (IVS11 þ 4251 T4A)) of the GSK3B gene were genotyped in 230 Chinese MDD patients and 415 controls. Among the MDD patients, 168 accepted selective serotonin reuptake inhibitor (SSRI) (fluoxetine or citalopram) antidepressant treatment and therapeutic evaluation for 4 weeks and 117 for 8 weeks. Significant association with MDD was not shown in the alleles and genotypes of single loci or four-locus haplotypes. However, three of the four polymorphisms investigated were significantly associated with 4-week antidepressant therapeutic effect (P ¼ 0.002-0.011). Of the four-locus haplotype analysis, the GSK3B TAGT carriers showed a poorer response to antidepressants in 4-week (Po0.0001) and 8-week (P ¼ 0.015) evaluation compared with other haplotype groups and would quite likely be the nonremitter to 8-week antidepressant treatment (P ¼ 0.006). Our findings show, for the first time, that GSK3B genetic variants play a role in the SSRI antidepressant therapeutic response and support the hypothesis that drugs regulating GSK3B activity may represent a novel treatment strategy for MDD.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

et al. 2008

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“…For example, lithium, GSK-3b knockout and other GSK-3 inhibitors show antidepressant effects in rodents. [39][40][41] Lithium and other GSK-3 inhibitors also attenuate the hyperactivity induced by amphetamine in rats 40 or dopamine transporter knockout in mice. 42 Valproic acid-induced promoter IV activation is mimicked by treatment with other HDAC inhibitors, SB and TSA, or by gene knockdown with HDAC1-specific siRNA (Figure 5), suggesting the involvement of HDAC inhibition.…”

Section: Discussionmentioning

confidence: 99%

The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons

et al. 2007

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Brain-derived neurotrophic factor (BDNF) has been strongly implicated in the synaptic plasticity, neuronal survival and pathophysiology of depression. Lithium and valproic acid (VPA) are two primary mood-stabilizing drugs used to treat bipolar disorder. Treatment of cultured rat cortical neurons with therapeutic concentrations of LiCl or VPA selectively increased the levels of exon IV (formerly rat exon III)-containing BDNF mRNA, and the activity of BDNF promoter IV. Surprisingly, lithium-or VPA-responsive element(s) in promoter IV resides in a region upstream from the calcium-responsive elements (CaREs) responsible for depolarization-induced BDNF induction. Moreover, activation of BDNF promoter IV by lithium or VPA occurred in cortical neurons depolarized with KCl, and deletion of these three CaREs did not abolish lithium-or VPA-induced activation. Lithium and VPA are direct inhibitors of glycogen synthase kinase-3 (GSK-3) and histone deacetylase (HDAC), respectively. We showed that lithium-induced activation of promoter IV was mimicked by pharmacological inhibition of GSK-3 or short interfering RNA (siRNA)-mediated gene silencing of GSK-3a or GSK-3b isoforms. Furthermore, treatment with other HDAC inhibitors, sodium butyrate and trichostatin A, or transfection with an HDAC1-specific siRNA also activated BDNF promoter IV. Our study demonstrates for the first time that GSK-3 and HDAC are respective initial targets for lithium and VPA to activate BDNF promoter IV, and that this BDNF induction involves a novel responsive region in promoter IV of the BDNF gene. Our results have strong implications for the therapeutic actions of these two mood stabilizers.

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“…Besides direct inhibition, lithium has been shown to indirectly inhibit GSK-3 through phosphorylation of GSK-3α at Ser21 and GSK-3β at Ser9 by multiple mechanisms including the activation of PKA (Jope, 1999a), phosphatidylinositol 3-kinase (PI3-K)-dependent AKT (Chalecka-Franaszek and Chuang, 1999), protein kinase C (PKC) (Kirshenboim et al, 2004), as well as the involvement of GSK-3 autoregulation Liang and Chuang, 2007). GSK-3 inhibition is also likely involved in the anti-depressant and anti-manic effects of lithium observed in rodent models (Gould et al, 2004;Kaidanovich-Beilin et al, 2004;O'Brien et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

Liang¹,

Wendland²,

Chuang³

2008

Molecular and Cellular Neuroscience

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Smad proteins are intracellular transducers for transforming growth factor-β (TGF-β signaling and play a critical role in differentiation, tissue repair and apoptosis of the central nervous system. Both TGF-β and its regulated gene, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in the etiology and progression of neurodegenerative diseases and mood disorders. We previously reported that GSK-3β protein depletion suppresses Smad3/4-dependent gene transcription and causes a reduction in PAI-1 expression. Here, we provide evidence that lithium, the drug for the treatment and prophylaxis of bipolar disorder, inhibits Smad-dependent signaling by regulating cAMP-protein kinase A (PKA), AKT-glycogen synthase kinase-3β (GSK-3β), and CRE-dependent signaling pathways in neuron-enriched cerebral cortical cultures of rats. We demonstrate that lithium-induced activation of these pathways inhibits Smad3/4-dependent gene transcription through an increase in pCREB Ser133 protein levels, an enhanced interaction between pCREB Ser133 and p300/CBP, which causes Smad3/4-p300/CBP complex disruption and transcriptional suppression of Smad3/4-dependent genes. Therapeutic implications of our findings are discussed.

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Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on β-catenin in mouse hippocampus

Cited by 260 publications

References 45 publications

Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

Glycogen synthase kinase-3β gene is associated with antidepressant treatment response in Chinese major depressive disorder

The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons

Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling

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