Fluoxetine induces alkalinization of astroglial cytosol through stimulation of sodium-hydrogen exchanger 1: dissection of intracellular signaling pathways

Ren, Jienan; Song, Dan; Bai, Qiufang; Verkhratsky, Alexei; Peng, Liang

doi:10.3389/fncel.2015.00061

Cited by 16 publications

(13 citation statements)

References 64 publications

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“…This is in agreement with our previously report (Ren et al 2015) although it contrasts the bi-phasic effect by chronic drug treatment. In addition, this stimulation lasted only for 40 min, and thereafter p-AKT level showed no significant difference from control group from 2 hours to 3 days (data not shown) after drug treatment.…”

Section: Page 10 Of 27 Psychopharmacologysupporting

confidence: 83%

“…Acute treatment with fluoxetine activates 5-HT 2B receptors in astroglia, which results in transactivation of epidermal growth factor receptor (EGFR) with subsequent recruitment of its intracellular signal pathways, MAPK/ERK and PI3K/AKT (Li et al 2008;Ren et al 2015). The glycogen synthase kinase 3 (GSK-3), the downstream substrate of AKT, is an enzyme, whcih has been initially discovered as a deactivator of glycogen synthase (GS) that converts glucose to glycogen.…”

Section: Introductionmentioning

confidence: 99%

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Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Bai

Song

et al. 2017

Psychopharmacology

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Here we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At lower concentrations fluoxetine down-regulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes. Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.

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Section: Page 10 Of 27 Psychopharmacologysupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Bai

Song

et al. 2017

Psychopharmacology

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“…Likewise, inhibition of astroglial plasmalemmal glutamate transporters also induced anhedonia (Bechtholt-Gompf et al ., 2010). Chronic treatment with antidepressants directly affected astroglia, by increasing expression of receptors and transporters responsible for CNS homeostasis and limiting glutamate release (Czeh and Di Benedetto, 2013; Dong et al ., 2015; Liu et al ., 2015; Ren et al ., 2015). In conclusion, mood disorders are associated with astrodegeneration and astroglial asthenia, which in turn affect brain homeostatic reserve and arguably synaptic transmission.…”

Section: Astroglia In Major Neuropsychiatric Diseasesmentioning

confidence: 99%

Translational potential of astrocytes in brain disorders

Verkhratsky

Steardo²,

Parpura

et al. 2016

Progress in Neurobiology

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Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

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“…; Ren et al . ). In astrocytic or C2C12 cells, there is crosstalk between PI3K/AKT and MAPK/ERK 1/2 (Pijet et al .…”

mentioning

confidence: 97%

“…; Ren et al . ), and these two signaling pathways both regulate the activation of STAT3 (Pijet et al . ; Liu et al .…”

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confidence: 99%

The ameliorative effect of fluoxetine on neuroinflammation induced by sleep deprivation

Xia

Yang

et al. 2018

Journal of Neurochemistry

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It is well known that sleep disorders are harmful to people's health and performance, and growing evidence suggests that sleep deprivation (SD) can trigger neuroinflammation in the brain. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is reported to be relevant to the neuroinflammation induced by SD, but the regulatory signaling that governs the NLRP3 inflammasome in SD is still unknown. Meanwhile, whether the regulatory action of antidepressants in astrocytes could affect the neuroinflammation induced by SD also remains obscure. In this study, we were the first to discover that the antidepressant fluoxetine, a type of specific serotonin reuptake inhibitor widely used in clinical practice, could suppress the neuroinflammation and neuronal apoptosis induced by SD. The main findings from this study are as follows: (i) SD stimulated the expression of activated NLRP3 inflammasomes and the maturation of IL-1β/18 via suppressing the phosphorylation of STAT3 in astrocytes; (ii) SD decreased the activation of AKT and stimulated the phosphorylation of GSK-3β, which inhibited the phosphorylation of STAT3; (iii) the NLRP3 inflammasome expression stimulated by SD was partly mediated by the P2X7 receptor; (iv) an agonist of STAT3 could significantly abolish the expression of NLRP3 inflammasomes induced by an agonist of the P2X7 receptor in primary cultured astrocytes; (v) the administration of fluoxetine could reverse the stimulation of NLRP3 inflammasome expression and function by SD through elevating the activation of STAT3. In conclusion, our present research suggests the promising possibility that fluoxetine could ameliorate the neuronal impairment induced by SD.

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Fluoxetine induces alkalinization of astroglial cytosol through stimulation of sodium-hydrogen exchanger 1: dissection of intracellular signaling pathways

Cited by 16 publications

References 64 publications

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

Translational potential of astrocytes in brain disorders

The ameliorative effect of fluoxetine on neuroinflammation induced by sleep deprivation

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