Increased cellular turnover in response to fluoxetine in neuronal precursors derived from human embryonic stem cells

Chang, Eun Ah; Beyhan, Zeki; Yoo, Myung Sik; Siripattarapravat, Kannika; Ko, Tak; Lookingland, Keith J.; Madhukar, Burra V.; Cibelli, José B.

doi:10.1387/ijdb.092851ec

Cited by 16 publications

(19 citation statements)

References 54 publications

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“…Fluoxetine has been reported to increase levels of neurogenesis (Chang, et al, 2010, Li, et al, 2009, Marcussen, et al, 2008, Perera, et al, 2011, Wang, et al, 2011) therefore we examined the effect of fluoxetine in the hippocampus sub-granular zone of the MBP1-hαsyn tg mice. Saline-treated MBP1-hαsyn tg mice display significantly reduced levels of doublecortin, a marker of neuroblasts (Figure 4A, C, E, p<0.05) and PCNA, a marker of proliferating cells in the sub-granular zone of the dentate gyrus (Figure 4F, H, J, p<0.05) in comparison to saline-treated non-tg mice, indicating reduced neurogenesis in the tg mice.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to its activity on the serotonergic system, fluoxetine has also been reported to have pro-proliferative activity (Chang, et al, 2010, Clark, et al, 2006, Wang, et al, 2011) and to effect levels of neurotrophic factors (NTFs) such as glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) (Allaman, et al, 2011, Chang, et al, 2010, Mercier, et al, 2004). A number of recent studies have also reported that fluoxetine can protect against 6-OHDA (6-hydroxydopamine) (Suzuki, et al, 2010) and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Chung, et al, 2011) induced damage in toxin-induced models of PD.…”

Section: Introductionmentioning

confidence: 99%

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Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy

Ubhi

Inglis

Mante

et al. 2012

Experimental Neurology

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The term α-synucleinopathies refers to a group of age-related neurological disorders including Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) that display an abnormal accumulation of alpha-synuclein (α-syn). In contrast to the neuronal α-syn accumulation observed in PD and DLB, MSA is characterized by a widespread oligodendrocytic α-syn accumulation. Transgenic mice expressing human α-syn under the oligodendrocyte-specific myelin basic protein promoter (MBP1-hαsyn tg mice) model many of the behavioral and neuropathological alterations observed in MSA. Fluoxetine, a selective serotonin reuptake inhibitor, has been shown to be protective in toxin-induced models of PD, however its effects in an in vivo transgenic model of α-synucleinopathy remain unclear. In this context, this study examined the effect of fluoxetine in the MBP1-hαsyn tg mice, a model of MSA. Fluoxetine adminstration ameliorated motor deficits in the MBP1-hαsyn tg mice, with a concomitant decrease in neurodegenerative pathology in the basal ganglia, neocortex and hippocampus. Fluoxetine adminstration also increased levels of the neurotrophic factors, GDNF (glial-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) in the MBP1-hαsyn tg mice compared to vehicle-treated tg mice. This fluoxetine-induced increase in GDNF and BDNF protein levels was accompanied by activation of the ERK signaling pathway. The effects of fluoxetine adminstration on myelin and serotonin markers were also examined. Collectively these results indicate that fluoxetine may represent a novel therapeutic intervention for MSA and other neurodegenerative disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy

Ubhi

Inglis

Mante

et al. 2012

Experimental Neurology

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“…The immunocytochemistry assay protocol was mostly as described in previous reports [24][25][26] RNA extraction and quantitative reverse transcription polymerase chain reaction analysis RNA was isolated and purified using the NucleoSpin RNA XS Total RNA Isolation Kit (Macherey-Nagle, Bethlehem, PA), following the manufacturer's instructions. We performed the reverse transcription polymerase chain reactions (RT-PCRs) as previously described [24,25].…”

Section: Immunocytochemistry Assaymentioning

confidence: 99%

“…We have described the BrdU incorporation assay protocol in a previously published report [26]. The nuclei were counterstained with Hoechst 33342 (1 mg/mL) for 5 min at room temperature.…”

Section: -Bromo-2-deoxyuridine Incorporation Assaymentioning

confidence: 99%

Generation of Leukemia Inhibitory Factor and Basic Fibroblast Growth Factor-Dependent Induced Pluripotent Stem Cells from Canine Adult Somatic Cells

Luo

Suhr

Chang

et al. 2011

Stem Cells and Development

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119

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For more than thirty years, the dog has been used as a model for human diseases. Despite efforts made to develop canine embryonic stem cells, success has been elusive. Here, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine adult fibroblasts, which we accomplished by introducing human OCT4, SOX2, c-MYC, and KLF4. The ciPSCs expressed critical pluripotency markers and showed evidence of silencing the viral vectors and normal karyotypes. Microsatellite analysis indicated that the ciPSCs showed the same profile as the donor fibroblasts but differed from cells taken from other dogs. Under culture conditions favoring differentiation, the ciPSCs could form cell derivatives from the ectoderm, mesoderm, and endoderm. Further, the ciPSCs required leukemia inhibitory factor and basic fibroblast growth factor to survive, proliferate, and maintain pluripotency. Our results demonstrate an efficient method for deriving canine pluripotent stem cells, providing a powerful platform for the development of new models for regenerative medicine, as well as for the study of the onset, progression, and treatment of human and canine genetic diseases.

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“…S5, H9 human ES cells were differentiated to NPCs as described [16]. H9-NPCs were propagated to passage 5 in iNC medium supplemented with 20 ng/mL FGF-2.…”

Section: Human Npc Culture and Neuron Derivationmentioning

confidence: 99%

Defining the Diversity of Phenotypic Respecification Using Multiple Cell Lines and Reprogramming Regimens

Alicea

Murthy

Keaton

et al. 2013

Stem Cells and Development

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To better understand the basis of variation in cellular reprogramming, we performed experiments with two primary objectives: first, to determine the degree of difference, if any, in reprogramming efficiency among cells lines of a similar type after accounting for technical variables, and second, to compare the efficiency of conversion of multiple similar cell lines to two separate reprogramming regimens-induced neurons and induced skeletal muscle. Using two reprogramming regimens, it could be determined whether converted cells are likely derived from a distinct subpopulation that is generally susceptible to reprogramming or are derived from cells with an independent capacity for respecification to a given phenotype. Our results indicated that when technical components of the reprogramming regimen were accounted for, reprogramming efficiency was reproducible within a given primary fibroblast line but varied dramatically between lines. The disparity in reprogramming efficiency between lines was of sufficient magnitude to account for some discrepancies in published results. We also found that the efficiency of conversion to one phenotype was not predictive of reprogramming to the alternate phenotype, suggesting that the capacity for reprogramming does not arise from a specific subpopulation with a generally ''weak grip'' on cellular identity. Our findings suggest that parallel testing of multiple cell lines from several sources may be needed to accurately assess the efficiency of direct reprogramming procedures, and that testing a larger number of fibroblast lines-even lines with similar origins-is likely the most direct means of improving reprogramming efficiency.

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Increased cellular turnover in response to fluoxetine in neuronal precursors derived from human embryonic stem cells

Cited by 16 publications

References 54 publications

Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy

Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy

Generation of Leukemia Inhibitory Factor and Basic Fibroblast Growth Factor-Dependent Induced Pluripotent Stem Cells from Canine Adult Somatic Cells

Defining the Diversity of Phenotypic Respecification Using Multiple Cell Lines and Reprogramming Regimens

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