Fluvoxamine and sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate induces the Ser473-phosphorylation of Akt-1 in PC12 cells

Nakano, Mayumi; Osada, Keizo; Misonoo, Atsushi; Fujiwara, Keisuke; Takahashi, Miho; Ogawa, Yasuaki; Haga, Toshiaki; Kanai, Shigeto; Tanaka, Daisuke; Sasuga, Y.; Yanagida, Takuyoh; Asakura, Mikio; Yamaguchi, Noboru

doi:10.1016/j.lfs.2009.11.017

Cited by 26 publications

(19 citation statements)

References 30 publications

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“…Treatment with the antidepressant fluvoxamine increased Akt-1 levels in PC12 cells (Nakano et al, 2010). The authors also showed that treatment with BDNF also stimulated phosphorylation of Akt-1, thus, both BDNF and Akt are interconnected (Nakano et al, 2010). Furthermore, elevated levels of Bcl-2 by FLX and OLZ in the present work may be involved in the activation of CREB via Akt signaling.…”

Section: Discussionsupporting

confidence: 63%

“…Also, Aubry et al (2009) demonstrated that OLZ regulated SH-SY5Y cell proliferation and survival, activated the Akt/GSK-3b axis and stimulated gene expression of Akt-1 mRNA and protein. Treatment with the antidepressant fluvoxamine increased Akt-1 levels in PC12 cells (Nakano et al, 2010). The authors also showed that treatment with BDNF also stimulated phosphorylation of Akt-1, thus, both BDNF and Akt are interconnected (Nakano et al, 2010).…”

Section: Discussionmentioning

confidence: 93%

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The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

Réus¹,

Abelaira²,

Agostinho³

et al. 2012

Journal of Psychiatric Research

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 93%

The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

Réus¹,

Abelaira²,

Agostinho³

et al. 2012

Journal of Psychiatric Research

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“…Indeed, fluvoxamine treatment stimulated Akt phosphorylation in vitro in PC12 cells (29). Our hypothesis regarding fluvoxamine-mediated Akt activation is supported by the fact that 1 R antagonists such as rimcazole (BW 234U) promote calcium-independent inhibition of phosphatidylinositol 3=-kinase (PI3K) signaling pathways, inhibiting Akt phosphorylation in tumor cell lines (45).…”

Section: Discussionmentioning

confidence: 71%

σ₁-Receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice

Tagashira

Bhuiyan

Shioda

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. Here, we investigated the role of σ1-receptor (σ1R) stimulation with fluvoxamine on myocardial hypertrophy and cardiac functional recovery. Male ICR mice were subjected to transverse aortic constriction (TAC) in the cardiac aortic arch. To confirm the cardioprotective role of fluvoxamine by σ1R stimulation, we treated mice with fluvoxamine (0.5 or 1 mg/kg) orally once per day for 4 wk after the onset of aortic banding. Interestingly, in untreated mice, σ1R expression in the left ventricle (LV) decreased significantly over the 4 wk as TAC-induced hypertrophy increased. In contrast, fluvoxamine administration significantly attenuated TAC-induced myocardial hypertrophy concomitant with recovery of σ1R expression in the LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV fractional shortening. The fluvoxamine cardioprotective effect was nullified by treatment with a σ1R antagonist [NE-100 (1 mg/kg)]. Importantly, another SSRI with very low affinity for σ1Rs, paroxetine, did not elicit antihypertrophic effects in TAC mice and cultured cardiomyocytes. Fluvoxamine treatment significantly restored TAC-induced impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in the LV. Our findings suggest that fluvoxamine protects against TAC-induced cardiac dysfunction via upregulated σ1R expression and stimulation of σ1R-mediated Akt-eNOS signaling in mice. This is the first report of a potential role for σ1R stimulation by fluvoxamine in attenuating cardiac hypertrophy and restoring contractility in TAC mice.

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“…It was indeed shown that antidepressants (imipramine) enhance the brain-derived neurotrophic factor signalling on the PLC-g/IP 3 /Ca 2 þ pathway via activation of the s 1 receptor in primary rat neuron cultures (Yagasaki et al, 2006). Moreover, Nakano et al (2010) directly demonstrated that the antidepressant (fluvoxamine) effect relied on a rapid increase in phosphorylation of Akt, as mimicked by brain-derived neurotrophic factor itself or by the s 1 receptor agonist DHEA sulfate. Our results, and the recent demonstration that both DHEA and pregnenolone sulfate prevented Ab 25-35 toxicity through a modulation of the PI3K/Akt/mTOR signalling Yang et al, 2012), confirmed the in vivo efficacy of s 1 ligand to modulate GSK-3b activity.…”

Section: The Mixed Muscarinic/r1 Ligand Anavex2-73 Prevent Tau Hyperpmentioning

confidence: 97%

Blockade of Tau Hyperphosphorylation and Aβ1–42 Generation by the Aminotetrahydrofuran Derivative ANAVEX2-73, a Mixed Muscarinic and σ1 Receptor Agonist, in a Nontransgenic Mouse Model of Alzheimer’s Disease

Lahmy

Meunier²,

Malmström³

et al. 2013

Neuropsychopharmacol

137

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The main objective of the present study was to establish whether the mixed s 1 /muscarinic ligand ANAVEX2-73, shown to be neuroprotective in Alzheimer's disease (AD) models in vivo and currently in clinical phase I/IIa, could have the ability to reduce the appearance of hyperphosphorylated Tau and amyloid-b 1-42 (Ab 1-42 ) in the Ab 25-35 mouse model of AD. We therefore first confirmed that Ab 25-35 injection induced hyperphosphorylation of Tau protein, by showing that it rapidly decreased Akt activity and activated glycogen synthase kinase-3b (GSK-3b) in the mouse hippocampus. Second, we showed that the kinase activation, and resulting Tau alteration, directly contributed to the amyloid toxicity, as co-administration of the selective GSK-3b inhibitor 2-thio(3-iodobenzyl)-5-(1-pyridyl)-[1,3,4]-oxidiazole blocked both Tau phosphorylation and Ab 25-35 -induced memory impairments. Third, we analyzed the ANAVEX2-73 effect on Tau phosphorylation and activation of the related kinase pathways (Akt and GSK-3b). And fourth, we also addressed the impact of the drug on Ab 25-35 -induced Ab 1-42 seeding and observed that the compound significantly blocked the increase in Ab 1-42 and C99 levels in the hippocampus, suggesting that it may alleviate amyloid load in AD models. The comparison with PRE-084, a selective and reference s 1 receptor agonist, and xanomeline, a muscarinic ligand presenting similar profile as ANAVEX2-73 on M1 and M2 subtypes, confirmed that both muscarinic and s 1 targets are involved in the ANAVEX2-73 effects. The drug, acting synergistically on both targets, but with moderate affinity, presents a promising pharmacological profile.

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Fluvoxamine and sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate induces the Ser473-phosphorylation of Akt-1 in PC12 cells

Cited by 26 publications

References 30 publications

The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

σ₁-Receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice

Blockade of Tau Hyperphosphorylation and Aβ1–42 Generation by the Aminotetrahydrofuran Derivative ANAVEX2-73, a Mixed Muscarinic and σ1 Receptor Agonist, in a Nontransgenic Mouse Model of Alzheimer’s Disease

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Fluvoxamine and sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate induces the Ser473-phosphorylation of Akt-1 in PC12 cells

Cited by 26 publications

References 30 publications

The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

The administration of olanzapine and fluoxetine has synergistic effects on intracellular survival pathways in the rat brain

σ1-Receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice

Blockade of Tau Hyperphosphorylation and Aβ1–42 Generation by the Aminotetrahydrofuran Derivative ANAVEX2-73, a Mixed Muscarinic and σ1 Receptor Agonist, in a Nontransgenic Mouse Model of Alzheimer’s Disease

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σ₁-Receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice