Person:
Liste-Noya, Isabel

First Name

Isabel

Last Name

Liste-Noya

Institution

ISCIII

Centrre

ISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)

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Now showing 1 - 10 of 25

Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation
(BioMed Central (BMC), 2021-03-18) Fernández Gil, Andrés; Quintana, Elena; Velasco, Patricia; Moreno-Jimenez, Belen; Andres, Belen de; Gaspar, Maria Luisa; Liste-Noya, Isabel; Vilar, Marçal; Mira, Helena; Cano, Eva; Ministerio de Economía y Competitividad (España)
Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process. We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation. Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1β, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1β) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1β expression is further augmented in aged SAMP8 compared to control SAMR1. Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.
DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain
(Wiley, 2015-12) Quintana, Elena; Fernandez-Ramos, Andres; Velasco, Patricia; Andres, Belen de; Liste-Noya, Isabel; Sancho, David; Gaspar, Maria Luisa; Cano, Eva; Instituto de Salud Carlos III; Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
The role and different origin of brain myeloid cells in the brain is central to understanding how the central nervous system (CNS) responds to injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) is a marker of specific DC subsets that share functional similarities, such as CD8α(+) DCs in lymphoid tissues and CD103(+) CD11b(low) DCs in peripheral tissues. Here, we analyzed the presence of DNGR-1 in DCs present in the mouse brain (bDCs). Dngr-1/Clec9a mRNA is expressed mainly in the meningeal membranes and choroid plexus (m/Ch), and its expression is enhanced by fms-like tyrosine kinase 3 ligand (Flt3L), a cytokine involved in DC homeostasis. Using Clec9a(egfp/egfp) mice, we show that Flt3L induces accumulation of DNGR-1-EGFP(+) cells in the brain m/Ch. Most of these cells also express major histocompatibility complex class II (MHCII) molecules. We also observed an increase in specific markers of cDC CD8α+ cells such as Batf-3 and Irf-8, but not of costimulatory molecules such as Cd80 and Cd86, indicating an immature phenotype for these bDCs in the noninjured brain. The presence of DNGR-1 in the brain provides a potential marker for the study of this specific brain cell subset. Knowledge and targeting of brain antigen presenting cells (APCs) has implications for the fight against brain diseases such as neuroinflammation-based neurodegenerative diseases, microbe-induced encephalitis, and brain tumors such as gliomas.
Impact of environmental neurotoxic: current methods and usefulness of human stem cells.
(Elsevier, 2020-12) Rosca, Andreea; Coronel Lopez, Raquel; Moreno, Miryam; Gonzalez-Martin-Niño, Rosa Maria; Oniga, Andreea; Martin, Alberto; López-Alonso, Victoria; González-Caballero, MCarmen; Liste-Noya, Isabel; Ministerio de Ciencia e Innovación (España); Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España)
The development of central nervous system is a highly coordinated and complex process. Any alteration of this process can lead to disturbances in the structure and function of the brain, which can cause deficits in neurological development, resulting in neurodevelopmental disorders, including, for example, autism or attention-deficit hyperactivity disorder. Exposure to certain chemicals during the fetal period and childhood is known to cause developmental neurotoxicity and has serious consequences that persist into adult life. For regulatory purposes, determination of the potential for developmental neurotoxicity is performed according the OECD Guideline 426, in which the test substance is administered to animals during gestation and lactation. However, these animal models are expensive, long-time consuming and may not reflect the physiology in humans; that makes it an unsustainable model to test the large amount of existing chemical products, hence alternative models to the use of animals are needed. One of the most promising methods is based on the use of stem cell technology. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into more specialized cell types. Because of these properties, these cells have gained increased attention as possible therapeutic agents or as disease models. Here, we provide an overview of the current models both animal and cellular, available to study developmental neurotoxicity and review in more detail the usefulness of human stem cells, their properties and how they are becoming an alternative to evaluate and study the mechanisms of action of different environmental toxicants.
Molecular effects of polystyrene nanoplastics on human neural stem cells
(Public Library of Science (PLOS), 2024) Martin-Folgar, Raquel; González-Caballero, MCarmen; Torres-Ruiz, Mónica; Cañas Portilla, Ana Isabel; De Alba-González, Mercedes; Liste-Noya, Isabel; Morales, Mónica
Nanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 μg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.
Background levels and brain organoid impact of RF field exposure in a healthcare environment
(Frontiers Media, 2024-03) Hernández, José A.; Rosca, Andreea; Suárez, Samuel; Coronel Lopez, Raquel; Suarez, Oscar J.; Peran-Ramos, Paula; Marina-Boillos, Pablo; Rabassa, Luis E.; Mateos-Martínez, Patricia; Liste-Noya, Isabel; López-Alonso, Victoria; Torres-Ruiz, Mónica; Febles, Victor M.; Ramos-Gonzalez, Maria Victoria; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Agencia Estatal de Investigación (España)
Introduction: This study is an introduction to the empirical and impact evaluation of radiofrequency electromagnetic field (RF-EMF) radiation exposure in a healthcare environment, focusing on an indoor microenvironment. It explores the expression of various genes associated with cellular responses, cell proliferation, senescence, and apoptotic cell death. The assessment analyzes current personal mobile communications (2G-5G FR1), providing a clear understanding of RF-EMF exposure and compliance with regulatory limits. Methods: The signals from different wireless communication systems at Hospital Universitario de Canarias (HUC) in Tenerife, Canary Islands, Spain, were examined in 11 locations. Four measurement campaigns were performed with frequencyselective exposimeters (PEMs) and an EME Spy 200 MVG, and experimental electric field values were compared as a long-term exposition. The frequency with the highest contribution (2.174 V/m) observed (1840 MHz) in UMTS was selected for biological effects evaluation. Results: The study focuses on four locations with the highest exposure to communication systems (downlinks), analyzing the results to verify compliance with regulations that ensure the safety of patients, the general public, and healthcare workers. LTE B20 (DL), GSM+UMTS 900 (DL), GSM 1800 (DL), UMTS 2100 (DL), and LTE B7 (DL) exhibited relatively higher E/m values throughout the campaigns, and these values consistently remained below the ICNIRP reference levels, signifying a consistently low level of exposure. In addition, this work presents the biological effects on neural stem cells (NSCs) using 3D brain organoids (BOs) exposed to RF signals in a validated and commercial experimental setting: the Gigahertz Transverse Electromagnetic cell (GTEM). The GTEM allows for the creation of homogeneous field electromagnetic fields in a small, enclosed setting and guarantees exposure conditions in a wide range of frequencies. BOs are an in vitro 3D cell-culture technology that reproduces the cellular composition and structure of the developing brain. Analyzing the expression of several genes associated with cellular responses, cell proliferation, senescence, and apoptotic cell death,wefound that exposure of BOs at 1840MHzdid not affectmRNAexpression in brain genes related to apoptosis or senescence. However, a decrease in gene expression for cell proliferation and cell activity markers was observed during the differentiation stage of BOs. Discussion: The discussion emphasizes the coexistence and evolution of various heterogeneous networks and services throughout the four measurement campaigns. Across all measured results, the levels of the obtained E-field were consistently well below the exposure limits set by internationally accepted standards and guidelines. These obtained values have been established in order to consider their potential effects on cell proliferation and cell activity, especially in differentiating biological organisms. Consequently, the results obtained and the methodology presented could serve as a foundational framework for establishing the basis of RF-EMF assessment in future heterogeneous 5G developments, particularly in the millimeter wave (mmWave) frequency range, where the forecast is for massive high-node density networks.
Stem cells as in vitro model of Parkinson's disease
(Hindawi, 2012-02) Martinez-Morales, Patricia L; Liste-Noya, Isabel
Progress in understanding neurodegenerative cell biology in Parkinson's disease (PD) has been hampered by a lack of predictive and relevant cellular models. In addition, the lack of an adequate in vitro human neuron cell-based model has been an obstacle for the uncover of new drugs for treating PD. The ability to generate induced pluripotent stem cells (iPSCs) from PD patients and a refined capacity to differentiate these iPSCs into DA neurons, the relevant disease cell type, promises a new paradigm in drug development that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSC that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSC can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling PD "in a dish" and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets, and enhance the probability of clinical success of new drugs.
A Two-Dimensional Human Minilung System (Model) for Respiratory Syncytial Virus Infections
(Multidisciplinary Digital Publishing Institute (MDPI), 2017-12-10) Magro-Lopez, Esmeralda; Guijarro, Trinidad; Martinez, Isidoro; Martin-Vicente, Maria; Liste-Noya, Isabel; Zambrano, Alberto; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España)
Human respiratory syncytial virus (HRSV) is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs). The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV-host interactions.
Oligomeric and Fibrillar Species of Aβ42 Diversely Affect Human Neural Stem Cells.
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-09-02) Bernabeu-Zornoza, Adela; Coronel Lopez, Raquel; Palmer, Charlotte; López-Alonso, Victoria; Liste-Noya, Isabel; Ministerio de Ciencia e Innovación (España); Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España)
Amyloid-β 42 peptide (Aβ1-42 (Aβ42)) is well-known for its involvement in the development of Alzheimer's disease (AD). Aβ42 accumulates and aggregates in fibers that precipitate in the form of plaques in the brain causing toxicity; however, like other forms of Aβ peptide, the role of these peptides remains unclear. Here we analyze and compare the effects of oligomeric and fibrillary Aβ42 peptide on the biology (cell death, proliferative rate, and cell fate specification) of differentiating human neural stem cells (hNS1 cell line). By using the hNS1 cells we found that, at high concentrations, oligomeric and fibrillary Aβ42 peptides provoke apoptotic cellular death and damage of DNA in these cells, but Aβ42 fibrils have the strongest effect. The data also show that both oligomeric and fibrillar Aβ42 peptides decrease cellular proliferation but Aβ42 oligomers have the greatest effect. Finally, both, oligomers and fibrils favor gliogenesis and neurogenesis in hNS1 cells, although, in this case, the effect is more prominent in oligomers. All together the findings of this study may contribute to a better understanding of the molecular mechanisms involved in the pathology of AD and to the development of human neural stem cell-based therapies for AD treatment.
Physiological and pathological effects of amyloid-β species in neural stem cell biology
(Medknow Publications, 2019-12) Bernabeu-Zornoza, Adela; Coronel Lopez, Raquel; Palmer, Charlotte; Monteagudo, Maria; Zambrano, Alberto; Liste-Noya, Isabel; Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; Ministerio de Economía y Competitividad (España); Comunidad de Madrid (España)
Although amyloid-β peptide is considered neurotoxic, it may mediate several physiological processes during embryonic development and in the adult brain. The pathological function of amyloid-β peptide has been extensively studied due to its implication in Alzheimer's disease, but its physiological function remains poorly understood. Amyloid-β peptide can be detected in non-aggregated (monomeric) and aggregated (oligomeric and fibrillary) forms. Each form has different cytotoxic and/or physiological properties, so amyloid-β peptide and its role in Alzheimer's disease need to be studied further. Neural stem cells and neural precursor cells are good tools for the study on neurodegenerative diseases and can provide future therapeutic applications in diseases such as Alzheimer's disease. In this review, we provide an outline of the effects of amyloid-β peptide, in monomeric and aggregated forms, on the biology of neural stem cells/neural precursor cells, and discuss the controversies. We also describe the possible molecular targets that could be implicated in these effects, especially GSK3β. A better understanding of amyloid-β peptide (both physiological and pathological), and the signaling pathways involved are essential to advance the field of Alzheimer's disease.
RNA-SEQ analysis reveals the implication of Amyloid Precursor Protein (APP) in cell fate specification of human neural Stem Cells by several Signaling Pathways. IBRO Neuroscience Reports
(Elsevier, 2023) Coronel Lopez, Raquel; Rosca, Andreea; González-Sastre, Rosa; Mateos-Martínez, Patricia; Gallego, Marta Ines; Liste-Noya, Isabel; López-Alonso, Victoria
Numerous studies have focused on the pathophysiological role of amyloid precursor protein (APP) in Alzheimer's disease (AD), being the aggregation of β-amyloid (Aβ) peptide a central event. However, many authors consider that alterations in physiological functions of APP are likely to play a key role in AD pathogenesis. APP is a glycoprotein expressed ubiquitously in a wide variety of tissues, being especially abundant in the brain. The APP expression is detected at early stages of nervous system development, as well as in adult brain, suggesting that this protein plays a key and important role at various stages of life. Previous studies in our laboratory revealed that APP playing an important role on differentiation of human neural stem cells (hNSCs), favoring glial differentiation (gliogenesis), and preventing the differentiation of them towards neuronal phenotype (neurogenesis). In that case, we proposed to the APP/AICD/GSK-3β system as a possible molecular mechanism involved in the observed effects. However, given the multifunctionality of APP, we think that other molecular mechanisms could also be implicated. In the present study, we have evaluated the effects of APP overexpression in hNSCs at a global level by a transcriptomic analysis using the massive RNA sequencing (RNA-seq) technology. Specifically, we have focused on differentially expressed genes (DEGs) that are related to neuronal and glial differentiation processes, as well as on groups of DEGs associated with different signaling pathways, to find a possible interaction between them and APP. Our data indicate a differential expression in genes related to gliogenesis and neurogenesis processes, as well as in the pathways of Notch signaling, Wnt signaling, PI3K-AKT signaling, and JAK-STAT signaling, among other. The knowledge of physiological functions of APP, as well as the possible signaling pathways that could be implicated, are essential to advance the understanding of the pathogenesis of AD.