Browsing by Subject "Neural stem cells"

Now showing 1 - 7 of 7
  • Thumbnail Image
    Publication
    Restricted
    Effects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells
    (2019-05-18) Motas, M; Sandoval, L; Rosca, A; Oniga, A; Zambrano, A; Ramos, JJ; González, MC; Liste, I; Ciencias Sociosanitarias
    Chlorpyrifos (CPF) is an organophosphate pesticide widely used in agriculture, whose traditional and wellknown mechanism of action is the inhibition of the enzyme Acetylcholinesterase (AChE). Subacute exposures to CPF have been associated with alterations different from the inhibition of AChE. Because of the vulnerability of the developing nervous system, prenatal and early postnatal exposures are of special concern. Human neural stem cells (hNSC) provide the opportunity to study early stages of neural development and may be a valuable tool for developmental neurotoxicology (DNT). In the current work, the cell line hNS1 was used as a model system with the aim of validating this cell line as a reliable testing method. To evaluate the effects of CPF on early developmental stages, hNS1 cells were exposed to different concentrations of the pesticide and cell death, proliferation and cell fate specification were analyzed under differentiation conditions. Since hNS1 cells responded to CPF in a similar way to other human cell lines, we consider it may be a valid model for DNT chemical assessment. CPF induced apoptotic cell death only at the highest doses tested, suggesting that it is not toxic for the specific developmental stage here addressed under short term exposure. In addition, the higher doses of CPF promoted the generation of astroglial cells, without affecting neurogenesis.
  • Thumbnail Image
    Publication
    Open Access
    In vitro and in vivo characterization of neural stem cells
    (Murcia : F. Hernández, 2004) Bazán, E.; Alonso, F.J.M.; Redondo, C.; López-Toledano, M.A.; Alfaro, J.M.; Reimers, D.; Herranz, A. S.; Paíno, C.L.; Serrano, A.B.; Cobacho, N.; Caso, E.; Lobo, M.V.T.
    Neural stem cells are defined as clonogenic cells with self-renewal capacity and the ability to generate all neural lineages (multipotentiality). Cells with these characteristics have been isolated from the embryonic and adult central nervous system. Under specific conditions, these cells can differentiate into neurons, glia, and non-neural cell types, or proliferate in long-term cultures as cell clusters termed “neurospheres”. These cultures represent a useful model for neurodevelopmental studies and a potential cell source for cell replacement therapy. Because no specific markers are available to unequivocally identify neural stem cells, their functional characteristics (self-renewal and multipotentiality) provide the main features for their identification. Here, we review the experimental and ultrastructural studies aimed at identifying the morphological characteristics and the antigenic markers of neural stem cells for their in vitro and in vivo identification.
  • Thumbnail Image
    Publication
    Open Access
    Leptomeninges: a novel stem cell niche harboring ischemia-induced neural progenitors
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Nakagomi, Takayuki; Nakano-Doi, Akiko; Matsuyama, Tomoiro
    It is well known that neural stem cells (NSCs) are present in many parts of the central nervous system (CNS), including the subventricular zone (SVZ) of the lateral ventricle, subgranular zone (SGZ) of the hippocampal dentate gyrus, cortex, and spinal cord. Using a mouse model of cortical infarction, we demonstrated for the first time that NSCs, which can differentiate into neural lineage cells, could be induced in the meninges (leptomeninges) of ischemic brain areas as well. However, such ischemia-induced NSCs (iNSCs) were not observed in the leptomeninges of non-ischemic areas. This suggests the leptomeninges, which surround the CNS, might be a novel stem cell niche harboring endogenous iNSCs following brain injury. In this review, we introduce the characterization and possible origin of leptomeningeal iNSCs based on our reports and recent findings. We also refer to the potential of leptomeningeal iNSCs for cortical neurogenesis.
  • Thumbnail Image
    Publication
    Open Access
    Melatonin promotes self-renewal and nestin expression in neural stem cells from the retina
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Gao, Yuhua; Ma, Li; Bai, Chunyu; Zhang, Xiangyang; Yang, Wancai
    Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promoting self-renewal in retinal stem cells remain unknown. We found that melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in retinal neural stem cells (NSCs) via melatonin receptor 1 (MT1). The ERK pathway inhibitor SCH772984 and TGF-β pathway inhibitor SB431542 were used to study the melatonin-mediated molecular mechanisms of cell proliferation in NSCs. The results revealed a novel molecular mechanism of melatonin promotion of self-renewal of NSCs in which a chain reaction in the ERK and TGF-β/Smad pathways promotes self-renewal and transcription of nestin. In addition, dual-luciferase assays revealed that Smad4 directly regulated nestin transcription after melatonin treatment in NSCs. These findings revealed novel mechanisms through which the ERK pathway cooperates with the Smad pathway to regulate self-renewal in NSCs to enhance nestin expression.
  • Thumbnail Image
    Publication
    Open Access
    Neural stem cell-mediated therapy for rare brain diseases: perspectives in the near future for LSDs and MNDs
    (Murcia: F. Hernández y J.F. Madrid, Universidad de Murcia, Departamento de Biología Celular e Histología, 2011) Filippis, Lidia de
    Lysosomal storage diseases (LSDs) are genetically inherited disorders affecting most patients in pediatric age and progressively lead to severe, even lethal, multiorgan dysfunction and brain neurodegeneration. Motor neuron diseases (MNDs) or Amyotrophic Lateral Sclerosis (ALS)-related syndromes are neurodegenerative disorders occurring in the majority of cases sporadically and affect adult middleaged patients. Despite being divergent in most pathological and physiological hallmarks, both MNDs and LSDs are characterized by tremendous clinical heterogeneity due to poor prognosis and variable onset of the symptoms. Moreover, both LSDs and MNDs are characterized by the concurrence of multiple pathogenetic processes, such as the development of inflammatory and excitotoxic environments. Furthermore, pharmacological, enzyme or genetic therapies have proven to be ineffective and no cure is currently available for the neurodegeneration in either LSD or ALS affected patients. Recent studies have identified non-neuronal cell types, such as astrocytes and microglia, as being involved in non cell-autonomous effects on MND or LSD progression. These findings have prompted the use of neural stem cells for the replacement of non-neuronal cells rather than neuronal cells, which may result in neuroprotection and immunomodulation. The choice of an appropriate tissue source and the establishment of standardized paradigms to culture human neural stem cells (hNSC) will allow their use for future clinical trials on both ALS and LSD affected patients and parallel drug screening studies with novel breakthroughs in the knowledge of neurodegenerative diseases.
  • Thumbnail Image
    Publication
    Open Access
    The regulation of stem cell aging by Wnt signaling
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko
    Aging is an inevitable physiological process that leads to the dysfunction of various tissues, and these changes may contribute to certain diseases, and ultimately death. Recent research has discovered biological pathways that promote aging. This review focuses on Wnt signaling, Wnt is a highly conserved secreted signaling molecule that plays an essential role in the development and function of various tissues, and is a notable factor that regulates aging. Although Wnt signaling influences aging in various tissues, its effects are particularly prominent in neuronal tissue and skeletal muscle. In neuronal tissue, neurogenesis is attenuated by the downregulation of Wnt signaling with aging. Skeletal muscle can also become weaker with aging, in a process known as sarcopenia. A notable cause of sarcopenia is the myogenic-to-fibrogenic transdifferentiation of satellite cells by excessive upregulation of Wnt signaling with aging, resulting in the impaired regenerative capacity of aged skeletal muscle. However, exercise is very useful for preventing the age-related alterations in neuronal tissue and skeletal muscle. Upregulation of Wnt signaling is implicated in the positive effects of exercise, resulting in the activation of neurogenesis in adult neuronal tissue and myogenesis in mature skeletal muscle. Although more investigations are required to thoroughly understand age-related changes and their biological mechanisms in a variety of tissues, this review proposes exercise as a useful therapy for the elderly, to prevent the negative effects of aging and maintain their quality of life.
  • Thumbnail Image
    Publication
    Open Access
    Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors
    (Cell Press, 2021-10-25) Jecrois, Emmanuelle S. ; Zheng, Wang ; Bornhorst, Miriam ; Li, Yinghua; Treisman, Daniel M. ; Muguyo, Daphine ; Huynh, Sharon ; Andrew, Shayne F.; Wang, Yuan ; Jiang, Jingwen ; Pierce, Brianna R. ; Mao, Hongmei ; Krause, Matthew K. ; Friend, Austin ; Steven F. Stasheff; Li, Wei ; Zong, Hui ; Packer, Roger J. ; Zhu, Yuan ; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
    The mechanism of vulnerability to pediatric low-grade gliomas (pLGGs)—the most common brain tumor in children—during development remains largely unknown. Using mouse models of neurofibromatosis type 1 (NF1)-associated pLGGs in the optic pathway (NF1-OPG), we demonstrate that NF1-OPG arose from the vulnerability to the dependency of Mek-Erk/MAPK signaling during gliogenesis of one of the two developmentally transient precursor populations in the optic nerve, brain-derived migrating glial progenitors (GPs), but not local progenitors. Hyperactive Erk/MAPK signaling by Nf1 loss overproduced GPs by disrupting the balance between stem-cell maintenance and gliogenesis of hypothalamic ventricular zone radial glia (RG). Persistence of RG-like GPs initiated NF1-OPG, causing Bax-dependent apoptosis in retinal ganglion cells. Removal of three Mek1/Mek2 alleles or transient post-natal treatment with a low-dose MEK inhibitor normalized differentiation of Nf1-/- RG-like GPs, preventing NF1-OPG formation and neuronal degeneration. We provide the proof-of-concept evidence for preventing pLGGs before tumor-associated neurological damage enters an irreversible phase.