Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

Abstract

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and β-tubulin were detected after neurogenesis as neural markers. Ten μM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

Transcription factor STOX1 regulates proliferation of inner ear epithelial cells via the AKT pathway

“…We found that after STOX1 knockdown in cultured epithelial cells, expression of markers for proliferation (PCNA and cyclin A, cyclin E) (26,42) was significantly reduced, but up-regulated following STOX1 over-expression. During mammalian organogenesis, the AKT pathway regulates both cell proliferation and programmed cell death (11,43). Our results further show that shSTOX1 inhibited phosphorylation of AKT in the inner ear utricular epithelial cells, while over-expression of STOX1 activated phosphorylation of AKT.…”

Sertraline increases the survival of retinoic acid induced neuronal cells but not glial cells from human mesenchymal stem cells

“…After 10 days (d) in culture, expanded cell populations were transferred into a medium consisting of DMEM (Gibco‐BRL) containing 10% FBS and 25 µg/mL gentamicin (Sigma, USA). The cells were pre‐treated with di‐methyl sulfoxide (DMSO, Sigma) and exposed to 10 −6 M all‐ trans RA (Sigma, USA) for 7 d as described previously (Rahmani et al, ). RA diluted in absolute ethanol was added to the culture medium twice a week.…”

“…On days 0, 7, and 14, total ribonucleic acid was extracted from cells using Trizol (Gibco, UK) (Rahmani et al, ). Reverse transcription was carried out with AMV reverse transcriptase (Takara, Japan) for 1 h at 42°C, followed by inactivation for 10 min at 95°C and cooling to 4°C.…”

“…Stem cells exhibit neuronal and glial phenotypes under selective culture conditions (Sanchez‐Ramos et al, ). Human endometrial stem cells (EnSCs) could also differentiate into cells bearing neuronal and glial phenotypes in culture after treatment with morphogens including retinoic acid (RA), neurotrophic factors, and β‐mercaptoethanol (Park et al, ; Rahmani et al, ; Rahmani et al, ). Since endometrial stem cells could be easily isolated and rapidly expanded from female patients without leading to major ethical and technical problems, they have great potential as therapeutic agents, as an autologous cell source (Schwab and Gargett, ; Shoae‐Hassani et al, ; Shoae‐Hassani et al, ; Shoae‐Hassani et al, ).…”

Reprogramming of endometrial adult stromal cells in the presence of a ROCK inhibitor, thiazovivin, could obtain more efficient iPSCs

“…Endometrial derived stromal cells from human endometrium were isolated and demonstrated the potential of differentiation into different lineage cells (Noureddini et al, ; Shoae‐Hassani et al, ,; Rahmani et al, ; Verdi et al, ). It has been shown that human endometrial cells express some levels of pluripotent factors (Kyo et al, ; Gotte et al, ), which, with additionally defined factors, result in significantly more efficient and accelerated generation of iPSCs compared with somatic cells (Park et al, ).…”