Activated Notch1 is a stronger astrocytic stimulus than leukemia inhibitory factor for rat neural stem cells

Rodríguez-Rivera, Nidia Samara; Molina‐Hernández, Anayansí; Sánchez-Cruz, Erika; Escalante‐Alcalde, Diana; Velasco, Iván

doi:10.1387/ijdb.092869nr

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…Mechanistically, LIF activates STAT3 in concert with retinoic acid (RA) and BMP2, which leads to the expression of glial fibrillary acidic protein (GFAP) (Fukushima et al, 2009). Additionally, the Notch pathway via Notch1-ICD and its downstream target Hes5 could induce AC differentiation even more efficiently (Rodriguez-Rivera et al, 2009). As mentioned previously in the present review, the Notch pathway plays a fundamental role in angiogenic sprouting and endothelial differentiation.…”

Section: Differentiation Of the Blood-brain Barrier And Phenotypic Chmentioning

confidence: 64%

Current concepts of blood-brain barrier development

Liebner¹,

Czupalla²,

Wolburg³

2011

Int. J. Dev. Biol.

201

149

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Homeostasis of the central nervous system (CNS) microenvironment is essential for its normal function and is maintained by the blood-brain barrier (BBB). The BBB proper is made up of endothelial cells (ECs) interconnected by tight junctions (TJs) that reveal a unique morphology and biochemical composition of the body's vasculature. In this article, we focus on developmental aspects of the BBB and describe morphological as well as molecular special features of the neurovascular unit (NVU) involved in barrier induction. Recently, we and others identified the Wnt/bcatenin pathway as crucial for brain angiogenesis, TJ and BBB formation. Based on these findings we discuss other pathways and molecular interactions for BBB establishment and maintenance. At the morphological level, our concept favors a major role for polarized astrocytes (ACs) therein. Orthogonal arrays of particles (OAPs) that are the morphological correlate of the water channel protein aquaporin-4 (AQP4) are specifically formed in the membrane of the AC endfoot. The polarized AC endfoot and hence OAPs are dependent on agrin and dystroglycan, of which agrin is a developmentally regulated extracellular matrix (ECM) component. Understanding the mechanisms leading to BBB development will be key to the understanding of barrier maintenance that is crucial for, but frequently disturbed, in the diseased adult brain.

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Section: Differentiation Of the Blood-brain Barrier And Phenotypic Chmentioning

confidence: 64%

Current concepts of blood-brain barrier development

Liebner¹,

Czupalla²,

Wolburg³

2011

Int. J. Dev. Biol.

201

149

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“…With these experiments, we aimed to identify possible signaling pathways involved in sAPPα function. Previous studies implicate the IL-6/gp130 pathway and the activity of Notch1 intracellular domain (NICD, activated Notch1) in glial differentiation of NSCs (Kwak et al, 2010; Rodriguez-Rivera et al, 2009). IL-6 concentrations in cortical brain homogenates from 3-month-old WT ( n = 4♂) and TgsAPPα ( n = 4♂) mice were measured by ELISA.…”

Section: Resultsmentioning

confidence: 99%

“…The sAPPα fragment may not be directly binding to the receptors that trigger either the IL-6 or Notch1 pathways; however, these findings imply that other sAPPα binding partners exist. Velasco et al reported that stimulation of glial differentiation in rat NSCs via the Notch1 pathway is more potent than stimulation via the IL-6/gp130 activated pathway (Rodriguez-Rivera et al, 2009). Our results suggest that sAPPα can promote glial cell fate of murine neural cells.…”

Section: Discussionmentioning

confidence: 99%

“…The gp130 pathway cooperates with the Notch1 pathway, which also enhances NSC commitment to glial fate by suppressing neuronal differentiation (Bhattacharya et al, 2008; Rodriguez-Rivera et al, 2009; Sugaya 2008). There is also evidence of crosstalk between the Notch1 and gp130 pathways as increased Hairy and enhancer of split (Hes), resulting from Notch1 activation, promotes phosphorylation of signal transducer and activator of transcription 3 (STAT3), a transcription factor for GFAP (Grandbarbe et al, 2003; Nagao et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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GFAP expression and social deficits in transgenic mice overexpressing human sAPPα

Bailey

Hou

Song

et al. 2013

Glia

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Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed β-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.

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“…Isolation of NPC cultures from the forebrains of E14 Wistar rat embryos was performed as previously described [44], [45]. The isolated cells were seeded at 1−1.5×10 6 in 10-cm diameter culture dishes previously treated with 15 µg/ml poly-L-ornithine (Sigma), and 1 µg/ml human Fibronectin (Invitrogen) in N2 medium (DMEM/F12 1:1, supplemented with 25 µg/l of human insulin, 30 nM sodium selenite, 100 µM putrescine, 20 nM progesterone and 100 mg/l Apotransferrin) with 10 ng/ml of Fibroblast growth factor 2 (FGF2; Peprotech) to promote proliferation, and were incubated at 37°C in a 5% of CO 2 environment.…”

Section: Methodsmentioning

confidence: 99%

Activin A Promotes Neuronal Differentiation of Cerebrocortical Neural Progenitor Cells

2012

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BackgroundActivin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive.Methodology/Principal FindingsWe studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocation of Smad 2/3 were induced. In proliferating NPC, Activin produced a significant decrease in cell area and also a discrete increase in the number of neurons in the presence of the mitogen Fibroblast Growth Factor 2. The percentages of cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods, Activin treatment produced further increases in the proportion of neurons, excluding premature cell cycle exit. In clonal assays, Activin significantly increased neuronal numbers per colony, supporting an instructive role. Activin-induced neurogenesis was dependent on activation of its receptors, since incubation with the type I receptor inhibitor SB431542 or the ligand-trap Follistatin prevented neuronal differentiation. Interestingly, SB431542 or Follistatin by themselves abolished neurogenesis and increased astrogliogenesis, to a similar extent to that induced by Bone Morphogenetic Protein (BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiation to control levels.ConclusionsOur results show an instructive neuronal effect of Activin A in cortical NPC in vitro, pointing out to a relevant role of this cytokine in the specification of NPC towards a neuronal phenotype.

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Activated Notch1 is a stronger astrocytic stimulus than leukemia inhibitory factor for rat neural stem cells

Cited by 14 publications

References 31 publications

Current concepts of blood-brain barrier development

Current concepts of blood-brain barrier development

GFAP expression and social deficits in transgenic mice overexpressing human sAPPα

Activin A Promotes Neuronal Differentiation of Cerebrocortical Neural Progenitor Cells

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