Transforming Growth Factor-β1 Is a Negative Modulator of Adult Neurogenesis

Wachs, Frank-Peter; Winner, Beate; Couillard‐Després, Sébastien; Schiller, Thorsten; Aigner, Robert; Winkler, Jürgen; Bogdahn, Ulrich; Aigner, Ludwig

doi:10.1097/01.jnen.0000218444.53405.f0

Cited by 155 publications

(169 citation statements)

References 72 publications

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“…Although a variety of growth and trophic factors are upregulated following ischemic injury, some are stimulators of neural progenitor proliferation, whereas others block the self-renewal of cells. For example, TGF␤1 can directly block cell division 42 by upregulating the expression of cell cycle inhibitors, whereas migration of cells away from their mitogenic niche can also promote cell cycle exit and inhibit cell division. 8 It is important to note that ischemia-induced migration of neuroblasts has been shown to be due to the expression of MCP-1, 44 which can attract the progenitor cells away from the neurogenic niche, blocking their proliferation.…”

Section: Role Of Neural Stem Cellsmentioning

confidence: 99%

Growth factors, stem cells, and stroke

Kalluri

Dempsey

2008

FOC

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✓ Postischemic neurogenesis has been identified as a compensatory mechanism to repair the damaged brain after stroke. Several factors are released by the ischemic tissue that are responsible for proliferation, differentiation, and migration of neural stem cells. An understanding of their roles may allow future therapies based on treatment with such factors. Although damaged cells release a variety of factors, some of them are stimulatory whereas some are inhibitory for neurogenesis. It is interesting to note that factors like insulin-like growth factor–I can induce proliferation in the presence of fibroblast growth factor–2 (FGF-2), and promote differentiation in the absence of FGF-2. Meanwhile, factors like transforming growth factor–β can induce the differentiation of neurons while inhibiting the proliferation of neural stem cells. Therefore, understanding the role of each factor in the process of neurogenesis will help physicians to enhance the endogenous response and improve the clinical outcome after stroke. In this article the authors discuss the role of growth factors and stem cells following stroke.

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Section: Role Of Neural Stem Cellsmentioning

confidence: 99%

Growth factors, stem cells, and stroke

Kalluri

Dempsey

2008

FOC

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“…Acute up-regulation of TGFβ1 after brain injury may be beneficial due to its positive effect on neurogenesis 50,51 . However, when TGFβ1 expression levels remain chronically elevated, it may affect the cell cycle of neural progenitor cells and inhibit neurogenesis by prolonging G1 and/or increasing cell cycle exit 49,52 . A similar effect on neurogenesis occurs during normal mammalian CNS development, when TGFβ has been reported to inhibit neural stem cell proliferation.…”

Section: Molecular Pathways and Tumorigenesismentioning

confidence: 99%

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Rodini

Suzuki

Nakahata

et al. 2010

Arq. Neuro-Psiquiatr.

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Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio-and chemoresistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFb, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers. Key words: medulloblastoma, neurobiology, signal transduction, stem cells, transforming growth factor beta, biological therapy.Vias de sinalização aberrantes no meduloblastoma: uma conexão com célula-tronco RESUMO Meduloblastoma é um tumor maligno do sistema nervoso central (SNC). Na infância, representa o tumor sólido mais frequente e a principal causa de morte relacionada ao câncer. Tratamentos atuais incluem cirurgia, quimioterapia e radioterapia, que podem trazer prejuízos cognitivos e desenvolvimento de tumores secundários. Novas perspectivas terapêuticas surgem com a identificação de células-tronco em gliomas, as quais apresentam alto potencial tumorigênico e maior resistência à radioterapia e quimioterapia. A hipótese das células-tronco tumorais sugere que a transformação de células-tronco e/ou progenitores neurais do cerebelo está envolvida no desenvolvimento do meduloblastoma. Portanto, analisar alterações genéticas e moleculares envolvidas nesse processo é de grande importância na pesquisa básica e aplicada ao câncer. Nesse sentido, discutimos o possível envolvimento de vias de sinalização bioquímica críticas a ambos os processos de

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“…In this regard, we and others reported that intracerebroventricular infusions of TGF-b into the rat brain or overexpression of TGF-b in transgenic mice resulted in a marked downregulation of cell proliferation and neurogenesis in the hippocampus. 57,58 Moreover, levels of TGF-b are known to be increasing in the brain along with ageing. 59,60 Additional experiments targeting specifically the individual signaling systems are required to elucidate in the age-dependent loss of fluoxetine activities on neurogenesis.…”

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confidence: 99%

Ageing abolishes the effects of fluoxetine on neurogenesis

et al. 2009

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Depression constitutes a widespread condition observed in elderly patients. Recently, it was found that several drugs employed in therapies against depression stimulate hippocampal neurogenesis in young rodents and nonhuman primates. As the rate of neurogenesis is dramatically reduced during ageing, we examined the influences of ageing on neurogenic actions of antidepressants. We tested the impact of fluoxetine, a broadly used antidepressant, on hippocampal neurogenesis in mice of three different age groups (100, 200 and over 400 days of age). Proliferation and survival rate of newly generated cells, as well as the percentage of cells that acquired a neuronal phenotype were analyzed in the hippocampus of mice that received fluoxetine daily in a chronic manner. Surprisingly, the action of fluoxetine on neurogenesis was decreasing as a function of age and was only significant in young animals. Hence, fluoxetine increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age). The data indicate that the action of fluoxetine on neurogenesis is highly dependent on the age of the treated individual. Although the function of neurogenesis in the clinical manifestation of depression is currently a matter of speculation, this study clearly shows that the therapeutic effects of antidepressants in elderly patients are not mediated by neurogenesis modulation.

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Transforming Growth Factor-β1 Is a Negative Modulator of Adult Neurogenesis

Cited by 155 publications

References 72 publications

Growth factors, stem cells, and stroke

Growth factors, stem cells, and stroke

Aberrant signaling pathways in medulloblastomas: a stem cell connection

Ageing abolishes the effects of fluoxetine on neurogenesis

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