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Fluoxetine regulates neurogenesis in vitro through modulation of GSK-3β/β-catenin signaling.

Hui J, Zhang J, Kim H, Tong C, Ying Q, Li Z, Mao X, Shi G, Yan J, Zhang Z, Xi G - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine.The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635.The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT1A receptor activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs Hui and Yan); Department of Neurology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs J Zhang, Li, Mao, Shi, and Xi); Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA (Drs Kim, Tong, and Ying); Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China (Dr Z Zhang).

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Fluoxetine treatment of 1 μM had no effect on cell differentiation or apoptosis of NPCs. (A) After 7 days cultured in differentiation condition, cells were collected for immunostaining detection. βIII-tubulin- and GFAP-positive cells were shown green and red, respectively. Blue DAPI staining showed the nuclei. Scale bars = 20 μm. (B) Quantitative analyses of βIII-tubulin- and GFAP-positive cells. The percentages of positive cells were shown. Values represent means ± SD (n = 6). (C) After 48h incubation, NPCs were used for TUNEL/DAPI staining. TUNEL-positive cells were green. Scale bars = 20 μm. (D) Quantitative analyses of TUNEL-positive cells. Values represent means ± SD (n = 6). DAPI, 4,6-diamidino-2-phenylindole; GFAP, anti-glial fibrillary acidic protein; NPCs, neural precursor cells; SD, standard deviation; TUNEL, transferase-mediated dUTP nick end labeling.
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Figure 2: Fluoxetine treatment of 1 μM had no effect on cell differentiation or apoptosis of NPCs. (A) After 7 days cultured in differentiation condition, cells were collected for immunostaining detection. βIII-tubulin- and GFAP-positive cells were shown green and red, respectively. Blue DAPI staining showed the nuclei. Scale bars = 20 μm. (B) Quantitative analyses of βIII-tubulin- and GFAP-positive cells. The percentages of positive cells were shown. Values represent means ± SD (n = 6). (C) After 48h incubation, NPCs were used for TUNEL/DAPI staining. TUNEL-positive cells were green. Scale bars = 20 μm. (D) Quantitative analyses of TUNEL-positive cells. Values represent means ± SD (n = 6). DAPI, 4,6-diamidino-2-phenylindole; GFAP, anti-glial fibrillary acidic protein; NPCs, neural precursor cells; SD, standard deviation; TUNEL, transferase-mediated dUTP nick end labeling.

Mentions: When the NPCs were incubated with medium containing FBS, the cells were able to spontaneously differentiate into neurons and gliocytes, as revealed by immunocytochemical analysis (Figure 2A). After 7 days in pro-differentiation conditions, the percentages of NPCs that differentiated into neurons and gliocytes in the control group were 23.17±3.76% and 61.83±4.83%. Similarly, the percentages of NPCs that differentiated into neurons and glia in fluoxetine treatment group were 24.00±3.22% and 61.33±5.72%. After a t-test was performed, no significant difference (p > 0.05, n = 6) was found between the two groups in terms of the percentage of neuronal and glial cells in each culture (Figure 2B).


Fluoxetine regulates neurogenesis in vitro through modulation of GSK-3β/β-catenin signaling.

Hui J, Zhang J, Kim H, Tong C, Ying Q, Li Z, Mao X, Shi G, Yan J, Zhang Z, Xi G - Int. J. Neuropsychopharmacol. (2014)

Fluoxetine treatment of 1 μM had no effect on cell differentiation or apoptosis of NPCs. (A) After 7 days cultured in differentiation condition, cells were collected for immunostaining detection. βIII-tubulin- and GFAP-positive cells were shown green and red, respectively. Blue DAPI staining showed the nuclei. Scale bars = 20 μm. (B) Quantitative analyses of βIII-tubulin- and GFAP-positive cells. The percentages of positive cells were shown. Values represent means ± SD (n = 6). (C) After 48h incubation, NPCs were used for TUNEL/DAPI staining. TUNEL-positive cells were green. Scale bars = 20 μm. (D) Quantitative analyses of TUNEL-positive cells. Values represent means ± SD (n = 6). DAPI, 4,6-diamidino-2-phenylindole; GFAP, anti-glial fibrillary acidic protein; NPCs, neural precursor cells; SD, standard deviation; TUNEL, transferase-mediated dUTP nick end labeling.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 2: Fluoxetine treatment of 1 μM had no effect on cell differentiation or apoptosis of NPCs. (A) After 7 days cultured in differentiation condition, cells were collected for immunostaining detection. βIII-tubulin- and GFAP-positive cells were shown green and red, respectively. Blue DAPI staining showed the nuclei. Scale bars = 20 μm. (B) Quantitative analyses of βIII-tubulin- and GFAP-positive cells. The percentages of positive cells were shown. Values represent means ± SD (n = 6). (C) After 48h incubation, NPCs were used for TUNEL/DAPI staining. TUNEL-positive cells were green. Scale bars = 20 μm. (D) Quantitative analyses of TUNEL-positive cells. Values represent means ± SD (n = 6). DAPI, 4,6-diamidino-2-phenylindole; GFAP, anti-glial fibrillary acidic protein; NPCs, neural precursor cells; SD, standard deviation; TUNEL, transferase-mediated dUTP nick end labeling.
Mentions: When the NPCs were incubated with medium containing FBS, the cells were able to spontaneously differentiate into neurons and gliocytes, as revealed by immunocytochemical analysis (Figure 2A). After 7 days in pro-differentiation conditions, the percentages of NPCs that differentiated into neurons and gliocytes in the control group were 23.17±3.76% and 61.83±4.83%. Similarly, the percentages of NPCs that differentiated into neurons and glia in fluoxetine treatment group were 24.00±3.22% and 61.33±5.72%. After a t-test was performed, no significant difference (p > 0.05, n = 6) was found between the two groups in terms of the percentage of neuronal and glial cells in each culture (Figure 2B).

Bottom Line: The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine.The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635.The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT1A receptor activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs Hui and Yan); Department of Neurology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs J Zhang, Li, Mao, Shi, and Xi); Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA (Drs Kim, Tong, and Ying); Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China (Dr Z Zhang).

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Related in: MedlinePlus