Effects of FTY720 (Fingolimod) on Proliferation, Differentiation, and Migration of Brain‐Derived Neural Stem Cells

Tan, Botao; Luo, Ze-Ru-Xin; Yan, Yue; Liu, Yuan; Li, Pan; Yu, Lehua; Yin, Ying

doi:10.1155/2016/9671732

Cited by 23 publications

(26 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a high concentration of 100 nM, FTY720 has a stronger proliferation and migration effect on NPs (Tan et al, 2016). Filamentous actin (F actin) polymerization is required for cell migration (Wang et al, 2016).…”

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

“…Filamentous actin (F actin) polymerization is required for cell migration (Wang et al, 2016). It has been demonstrated that increased NPs migration by FTY720 is due to up-regulation of F actin (Tan et al, 2016).…”

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

“…Remarkably, high 10-100 nM and low 0.01-1 nM concentrations of FTY720 respectively inhibited and induced NPs differentiation (Cipriani et al, 2017;Sun et al, 2016;Tan et al, 2016;Zhang et al, 2017) NPCs treated with FTY720 (100 nmol/L) • Increased MAP Kinase phosphorylation (Blanc et al, 2015) Human oligodendrocyte progenitor cells treated with FTY720 (different exposure times)…”

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

“…• Affected membrane elaboration (in a time-and dose-dependent manner) via S1P1 or S1P3/S1P5 • Affected remyelination (Miron, Hall, et al, 2008;Miron et al, 2010) doses (Tan et al, 2016;Zhang et al, 2017). Mechanistically, FTY720…”

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

See 3 more Smart Citations

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Yazdi

Ghasemi-Kasman

Javan

2019

J of Neuroscience Research

View full text Add to dashboard Cite

Fingolimod (FTY720) is a sphingosine 1‐phosphate (S1P) receptor analog, which has been approved as an oral immunomodulator for treating relapsing–remitting multiple sclerosis. This drug prevents lymphocyte egression from lymph nodes and reduces the infiltration of inflammatory mediators into the central nervous system. Based on its lipophilic nature, FTY720 passes through the blood–brain barrier and can directly affect neural cells. A notably different subtype of S1P receptors expresses in neural cells, which suggests FTY720 is a drug capable of affecting neural cells. Oligodendrocytes (OLs) are considered as the primary target cells in MS. Remyelination is a process including the proliferation of neural progenitors and oligodendrocyte precursor cells, their migration to the lesion site and their differentiation to mature oligodendrocytes. Experimental and clinical studies have described the impact of FTY720 on endogenous remyelination elements. In this review, we will explain the current clinical and experimental evidence that exists on the effects of FTY720 on remyelination and the underlying mechanisms.

show abstract

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

Section: The Effec T Of F T Y 72 0 On Myelin Reg Ener Ati On In Animentioning

confidence: 99%

See 2 more Smart Citations

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Yazdi

Ghasemi-Kasman

Javan

2019

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…FTY720 enhanced survival, proliferation and migration of NSCs in vitro [18–21]; however, effect on differentiation remains controversial. Our results, demonstrating a positive effect of FTY720 on differentiation of postnatal NSCs, both to neurons and oligodendrocytes, indicate that FTY720 is able to accelerate neurogenesis and oligodendrogenesis from neural precursors and suggest a potential neurogenic role also in vivo.…”

Section: Resultsmentioning

confidence: 99%

Effects of FTY720 on brain neurogenic niches in vitro and after kainic acid-induced injury

Cipriani

Chara

Rodríguez‐Antigüedad

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundFTY720 (fingolimod, Gilenya™) is an oral, blood-brain barrier (BBB)-passing drug approved as immunomodulatory treatment for relapsing-remitting form of the multiple sclerosis (MS). In addition, FTY720 exerts several effects in the central nervous system (CNS), ranging from neuroprotection to reduction of neuroinflammation. However, the neurogenic and oligodendrogenic potential of FTY720 has been poorly investigated. In this study, we assessed the effect of FTY720 on the production of new neurons and oligodendrocytes from neural stem/precursor cells both in vitro and in vivo.MethodsNeural stem cells (NSCs) derived from the young rat subventricular zone (SVZ) were exposed to FTY720 (10, 100 nM), and their differentiation into neurons and oligodendrocytes was measured using immunofluorescence for anti-β-III tubulin or CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase) as markers of mature neurons or oligodendrocytes, respectively. In addition, intracerebroventricular (icv) administration of kainic acid (KA; 0.5 μg/2 μl) in Sprague-Dawley rats was used as an in vivo model of neuronal death and inflammation. FTY720 was applied icv (1 μg/2 μl), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 8 days after KA injection. To visualize cell proliferation in the hippocampus and in white matter regions, rats were administered 5-bromo-2-deoxyuridine (BrdU) 100 mg/kg, ip injected every 2 days. Immunohistochemical analyses were performed on rat brain slices to measure the production of new neuronal precursors (doublecortin/DCX+ cells) and new oligodendrocytes precursors (proteoglycan/NG2+ cells).ResultsIn this study, we observed that FTY720 increased postnatal NSCs differentiation into both neurons and oligodendrocytes in vitro. In turn, in adult animals, FTY720 enhanced the percentage of BrdU+ cells coexpressing DCX marker, both in basal (FTY720 alone) and in neurodegenerative (FTY720 + KA) conditions. However, FTY720 had only a partial effect on proliferation and differentiation of oligodendrocyte progenitor cell (OPC) population in vivo.ConclusionsFTY720 promotes neurogenesis and oligodendrogenesis in vitro under basal conditions. In addition, it increases the generation of neuroblasts and oligodendrocytes after excitotoxic brain injury. This suggests that FTY720 has the potential to activate the neurogenic niche and thus favour tissue repair after lesion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0922-6) contains supplementary material, which is available to authorized users.

show abstract

Sphingosine 1‐phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer

Bao

Qian

et al. 2020

Glia

View full text Add to dashboard Cite

Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth‐promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1‐phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription‐PCR (RT‐PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes‐associated protein (YAP) was required for S1P‐induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.

show abstract

Effects of FTY720 (Fingolimod) on Proliferation, Differentiation, and Migration of Brain‐Derived Neural Stem Cells

Cited by 23 publications

References 32 publications

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

Effects of FTY720 on brain neurogenic niches in vitro and after kainic acid-induced injury

Sphingosine 1‐phosphate promotes the proliferation of olfactory ensheathing cells through YAP signaling and participates in the formation of olfactory nerve layer

Contact Info

Product

Resources

About