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873 results on '"Hol, Elly M."'

1. Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids

Author

van der Geest, Astrid T., Jakobs, Channa E., Ljubikj, Tijana, Huffels, Christiaan F. M., Cañizares Luna, Marta, Vieira de Sá, Renata, Adolfs, Youri, de Wit, Marina, Rutten, Daan H., Kaal, Marthe, Zwartkruis, Maria M., Carcolé, Mireia, Groen, Ewout J. N., Hol, Elly M., Basak, Onur, Isaacs, Adrian M., Westeneng, Henk-Jan, van den Berg, Leonard H., Veldink, Jan H., Schlegel, Domino K., and Pasterkamp, R. Jeroen

Published
2024
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6. Loss of lamin‐B1 and defective nuclear morphology are hallmarks of astrocyte senescence in vitro and in the aging human hippocampus

Author

Matias, Isadora, Diniz, Luan Pereira, Damico, Isabella Vivarini, Araujo, Ana Paula Bergamo, da Silva Neves, Laís, Vargas, Gabriele, Leite, Renata EP, Suemoto, Claudia K, Nitrini, Ricardo, Jacob‐Filho, Wilson, Grinberg, Lea T, Hol, Elly M, Middeldorp, Jinte, and Gomes, Flávia Carvalho Alcantara

Subjects
Biomedical and Clinical Sciences, Aging, Brain Disorders, Genetics, Neurosciences, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Animals, Astrocytes, Cellular Senescence, Hippocampus, Humans, Lamin Type B, Mice, aging, astrocyte, human and mouse hippocampus, lamin-B1, senescence, synapse, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The increase in senescent cells in tissues, including the brain, is a general feature of normal aging and age-related pathologies. Senescent cells exhibit a specific phenotype, which includes an altered nuclear morphology and transcriptomic changes. Astrocytes undergo senescence in vitro and in age-associated neurodegenerative diseases, but little is known about whether this process also occurs in physiological aging, as well as its functional implication. Here, we investigated astrocyte senescence in vitro, in old mouse brains, and in post-mortem human brain tissue of elderly. We identified a significant loss of lamin-B1, a major component of the nuclear lamina, as a hallmark of senescent astrocytes. We showed a severe reduction of lamin-B1 in the dentate gyrus of aged mice, including in hippocampal astrocytes, and in the granular cell layer of the hippocampus of post-mortem human tissue from non-demented elderly. The lamin-B1 reduction was associated with nuclear deformations, represented by an increased incidence of invaginated nuclei and loss of nuclear circularity in senescent astrocytes in vitro and in the aging human hippocampus. We also found differences in lamin-B1 levels and astrocyte nuclear morphology between the granular cell layer and polymorphic layer in the elderly human hippocampus, suggesting an intra-regional-dependent aging response of human astrocytes. Moreover, we described senescence-associated impaired neuritogenic and synaptogenic capacity of mouse astrocytes. Our findings show that reduction of lamin-B1 is a conserved feature of hippocampal cells aging, including astrocytes, and shed light on significant defects in nuclear lamina structure which may contribute to astrocyte dysfunctions during aging.

Published
2022

8. Reactive astrocyte nomenclature, definitions, and future directions

Author

Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P, Petzold, Gabor C, Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J, Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E, Bonvento, Gilles, Butt, Arthur M, Chen, Wei-Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E, Goldman, Steven A, Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G, Heiland, Dieter H, Hol, Elly M, Holt, Matthew G, Iino, Masamitsu, Kastanenka, Ksenia V, Kettenmann, Helmut, Khakh, Baljit S, Koizumi, Schuichi, Lee, C Justin, Liddelow, Shane A, MacVicar, Brian A, Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V, Murai, Keith K, Norris, Christopher M, Okada, Seiji, Oliet, Stéphane HR, Oliveira, João F, Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G, Pfrieger, Frank W, Poskanzer, Kira E, Quintana, Francisco J, Ransohoff, Richard M, Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R, Rothstein, Jeffrey D, Rouach, Nathalie, Rowitch, David H, Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A, Vitorica, Javier, Wanner, Ina-Beate, Wood, Levi B, Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R, Zorec, Robert, Sofroniew, Michael V, and Verkhratsky, Alexei

Subjects
Neurosciences, Brain Disorders, Neurological, Aging, Animals, Astrocytes, Brain, Brain Diseases, Brain Injuries, Humans, Spinal Cord, Spinal Cord Injuries, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

Published
2021

10. Structure-stiffness relation of live mouse brain tissue determined by depth-controlled indentation mapping

Author

Antonovaite, Nelda, Beekmans, Steven V., Hol, Elly M., Wadman, Wytse J., and Iannuzzi, Davide

Subjects
Physics - Biological Physics
Abstract

The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of isolated horizontal live mouse brain sections. Our results confirm the highly viscoelestic nature of the material and clearly show that the mechanical properties correlate with the different morphological layers of the samples investigated. Interestingly, the relative cell nuclei area seems to negatively correlate with the stiffness observed.

Published
2018

11. In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

Author

Meerwaldt, Anu E, Straathof, Milou, Oosterveld, Wija, van Heijningen, Caroline L, van Leent, Mandy MT, Toner, Yohana C, Munitz, Jazz, Teunissen, Abraham JP, Daemen, Charlotte C, van der Toorn, Annette, van Vliet, Gerard, van Tilborg, Geralda AF, De Feyter, Henk M, de Graaf, Robin A, Hol, Elly M, Mulder, Willem JM, and Dijkhuizen, Rick M

Published
2023
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14. Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease

Author

Fernández Zapata, Camila, Giacomello, Ginevra, Spruth, Eike J., Middeldorp, Jinte, Gallaccio, Gerardina, Dehlinger, Adeline, Dames, Claudia, Leman, Julia K. H., van Dijk, Roland E., Meisel, Andreas, Schlickeiser, Stephan, Kunkel, Desiree, Hol, Elly M., Paul, Friedemann, Parr, Maria Kristina, Priller, Josef, and Böttcher, Chotima

Published
2022
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22. Progesterone receptor distribution in the human hypothalamus and its association with suicide

Author

Translational Neuroscience, Brain, Cancer, Pathologie, Zhang, Lin, Verwer, Ronald W H, van Heerikhuize, Joop, Lucassen, Paul J, Nathanielsz, Peter W, Hol, Elly M, Aronica, Eleonora, Dhillo, Waljit S, Meynen, Gerben, Swaab, Dick F, Translational Neuroscience, Brain, Cancer, Pathologie, Zhang, Lin, Verwer, Ronald W H, van Heerikhuize, Joop, Lucassen, Paul J, Nathanielsz, Peter W, Hol, Elly M, Aronica, Eleonora, Dhillo, Waljit S, Meynen, Gerben, and Swaab, Dick F

Published
2024

23. Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma

Author

MS KNO, ZL Neuro-Oncologie Medisch, Neurochirurgie, Brain, Cancer, Tan, A Katherine, Henry, Aurelie, Goffart, Nicolas, van Logtestijn, Sofie, Bours, Vincent, Hol, Elly M, Robe, Pierre A, MS KNO, ZL Neuro-Oncologie Medisch, Neurochirurgie, Brain, Cancer, Tan, A Katherine, Henry, Aurelie, Goffart, Nicolas, van Logtestijn, Sofie, Bours, Vincent, Hol, Elly M, and Robe, Pierre A

Published
2024

24. Transcriptomic and morphological maturation of human astrocytes in cerebral organoids

Author

TN groep Hol, Brain, AIOS Psychiatrie, Translational Neuroscience, Regenerative Medicine and Stem Cells, Cancer, Verkerke, Marloes, Berdenis van Berlekom, Amber, Donega, Vanessa, Vonk, Daniëlle, Sluijs, Jacqueline A, Butt, Nayab F, Kistemaker, Lois, de Witte, Lot D, Pasterkamp, R Jeroen, Middeldorp, Jinte, Hol, Elly M, TN groep Hol, Brain, AIOS Psychiatrie, Translational Neuroscience, Regenerative Medicine and Stem Cells, Cancer, Verkerke, Marloes, Berdenis van Berlekom, Amber, Donega, Vanessa, Vonk, Daniëlle, Sluijs, Jacqueline A, Butt, Nayab F, Kistemaker, Lois, de Witte, Lot D, Pasterkamp, R Jeroen, Middeldorp, Jinte, and Hol, Elly M

Published
2024

25. Early amyloid-induced changes in microglia gene expression in male APP/PS1 mice

Author

TN groep Hol, Brain, Translational Neuroscience, Cancer, Projectafdeling ALS, Oshima, Takuya, Kater, Mandy S J, Huffels, Christiaan F M, Wesseling, Evelyn M, Middeldorp, Jinte, Hol, Elly M, Verheijen, Mark H G, Smit, August B, Boddeke, Erik W G M, Eggen, Bart J L, TN groep Hol, Brain, Translational Neuroscience, Cancer, Projectafdeling ALS, Oshima, Takuya, Kater, Mandy S J, Huffels, Christiaan F M, Wesseling, Evelyn M, Middeldorp, Jinte, Hol, Elly M, Verheijen, Mark H G, Smit, August B, Boddeke, Erik W G M, and Eggen, Bart J L

Published
2024

26. GFAP-isoforms in the nervous system: Understanding the need for diversity

Author

TN groep Hol, Brain, Translational Neuroscience, Cancer, de Reus, Alexandra J E M, Basak, Onur, Dykstra, Werner, van Asperen, Jessy V, van Bodegraven, Emma J, Hol, Elly M, TN groep Hol, Brain, Translational Neuroscience, Cancer, de Reus, Alexandra J E M, Basak, Onur, Dykstra, Werner, van Asperen, Jessy V, van Bodegraven, Emma J, and Hol, Elly M

Published
2024

27. Progesterone receptor distribution in the human hypothalamus and its association with suicide

Author

Forensische psychiatrie / psychologie, UCALL / Aansprakelijkheid en verantwoordelijkheid, Zhang, Lin, Verwer, Ronald W.H., van Heerikhuize, Joop, Lucassen, Paul J., Nathanielsz, Peter W., Hol, Elly M., Aronica, Eleonora, Dhillo, Waljit S., Meynen, Gerben, Swaab, Dick F., Forensische psychiatrie / psychologie, UCALL / Aansprakelijkheid en verantwoordelijkheid, Zhang, Lin, Verwer, Ronald W.H., van Heerikhuize, Joop, Lucassen, Paul J., Nathanielsz, Peter W., Hol, Elly M., Aronica, Eleonora, Dhillo, Waljit S., Meynen, Gerben, and Swaab, Dick F.

Published
2024

31. The Indispensable Roles of Microglia and Astrocytes during Brain Development

Author

Reemst, Kitty, Noctor, Stephen C, Lucassen, Paul J, and Hol, Elly M

Subjects
Brain Cancer, Neurosciences, Brain Disorders, Rare Diseases, Cancer, 1.1 Normal biological development and functioning, Underpinning research, Neurological, astrocytes, brain development, glial cells, microglia, neurodevelopmental disorders, Psychology, Cognitive Sciences, Experimental Psychology
Abstract

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease.

Published
2016

39. Safety and pharmacodynamic efficacy of eculizumab in aneurysmal subarachnoid hemorrhage (CLASH): A phase 2a randomized clinical trial

Author

Koopman, Inez, primary, Tack, Reinier WP, additional, Wunderink, Herman F, additional, Bruns, Anke HW, additional, van der Schaaf, Irene C, additional, Cianci, Daniela, additional, Gelderman, Kyra A, additional, van de Ridder, Inge M, additional, Hol, Elly M, additional, Rinkel, Gabriel JE, additional, and Vergouwen, Mervyn DI, additional

Published
2023
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45. Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma.

Author

Tan, A. Katherine, Henry, Aurelie, Goffart, Nicolas, van Logtestijn, Sofie, Bours, Vincent, Hol, Elly M., and Robe, Pierre A.

Subjects
GLIOMA treatment, CELL metabolism, IN vitro studies, REVERSE transcriptase polymerase chain reaction, IMMUNIZATION, ANIMAL experimentation, MACROPHAGES, KILLER cells, HISTOCOMPATIBILITY, TREATMENT effectiveness, LYMPHOCYTES, RESEARCH funding, MYELOID cells, IMMUNOTHERAPY, MICE
Abstract

Simple Summary: The major histocompatibility complex type II is downregulated in glioblastoma (GB) due to the silencing of the major transcriptional regulator class II transactivator (CIITA). Recent studies have posed CIITA as a possible target in treating patients with GB. However, our results show that in mice, vaccination experiments with wildtype (-WT) and CIITA-expressing cells (-CIITA) equivalently protect against subsequent intracerebral challenges with GL261 cells. Adoptive cell transfer experiments likewise showed a similar antitumor potential of lymphocytes harvested from mice implanted intracerebrally with GL261-WT or -CIITA. Human GB-infiltrating myeloid cells, lymphocytes and NK cells remained mostly inactivated and/or tumor-supportive when in co-culture with GB cells, regardless of CIITA. Altogether, these results question the therapeutic potential of CIITA-mediated immunotherapy in glioblastoma. Background: The major histocompatibility complex type II is downregulated in glioblastoma (GB) due to the silencing of the major transcriptional regulator class II transactivator (CIITA). We investigated the pro-immunogenic potential of CIITA overexpression in mouse and human GB. Methods: The intracerebral growth of wildtype GL261-WT cells was assessed following contralateral injection of GL261-CIITA cells or flank injections with GL261-WT or GL261-CIITA cells. Splenocytes obtained from mice implanted intracerebrally with GL261-WT, GL261-CIITA cells or phosphate buffered saline (PBS) were transferred to other mice and subsequently implanted intracerebrally with GL261-WT. Human GB cells and (syngeneic) GB-infiltrating immune cells were isolated from surgical samples and co-cultured with GB cells expressing CIITA or not, followed by RT-qPCR assessment of the expression of key immune regulators. Results: Intracerebral vaccination of GL261-CIITA significantly reduced the subsequent growth of GL261-WT cells implanted contralaterally. Vaccination with GL261-WT or -CIITA subcutaneously, however, equivalently retarded the intracerebral growth of GL261 cells. Adoptive cell transfer experiments showed a similar antitumor potential of lymphocytes harvested from mice implanted intracerebrally with GL261-WT or -CIITA. Human GB-infiltrating myeloid cells and lymphocytes were not activated when cultured with CIITA-expressing GB cells. Tumor-infiltrating NK cells remained mostly inactivated when in co-culture with GB cells, regardless of CIITA. Conclusion: these results question the therapeutic potential of CIITA-mediated immunotherapy in glioblastoma. [ABSTRACT FROM AUTHOR]

Published
2024
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47. In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging

Author

Meerwaldt, Anu E., Straathof, Milou, Oosterveld, Wija, van Heijningen, Caroline L., van Leent, Mandy M.T., Toner, Yohana C., Munitz, Jazz, Teunissen, Abraham J.P., Daemen, Charlotte C., van der Toorn, Annette, van Vliet, Gerard, van Tilborg, Geralda A.F., De Feyter, Henk M., de Graaf, Robin A., Hol, Elly M., Mulder, Willem J.M., Dijkhuizen, Rick M., Meerwaldt, Anu E., Straathof, Milou, Oosterveld, Wija, van Heijningen, Caroline L., van Leent, Mandy M.T., Toner, Yohana C., Munitz, Jazz, Teunissen, Abraham J.P., Daemen, Charlotte C., van der Toorn, Annette, van Vliet, Gerard, van Tilborg, Geralda A.F., De Feyter, Henk M., de Graaf, Robin A., Hol, Elly M., Mulder, Willem J.M., and Dijkhuizen, Rick M.

Abstract

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium (2H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue.

Published
2023

48. Safety and pharmacodynamic efficacy of eculizumab in aneurysmal subarachnoid hemorrhage (CLASH): A phase 2a randomized clinical trial

Author

Opleiding Neurologie, Projectafdeling CVZ, MMB opleiding Arts microbioloog, Infection & Immunity, MS Radiologie, Brain, Circulatory Health, CTM & Statistical consultation, Translational Neuroscience, Cancer, Neurologen, Koopman, Inez, Tack, Reinier Wp, Wunderink, Herman F, Bruns, Anke Hw, van der Schaaf, Irene C, Cianci, Daniela, Gelderman, Kyra A, van de Ridder, Inge M, Hol, Elly M, Rinkel, Gabriel Je, Vergouwen, Mervyn DI, Opleiding Neurologie, Projectafdeling CVZ, MMB opleiding Arts microbioloog, Infection & Immunity, MS Radiologie, Brain, Circulatory Health, CTM & Statistical consultation, Translational Neuroscience, Cancer, Neurologen, Koopman, Inez, Tack, Reinier Wp, Wunderink, Herman F, Bruns, Anke Hw, van der Schaaf, Irene C, Cianci, Daniela, Gelderman, Kyra A, van de Ridder, Inge M, Hol, Elly M, Rinkel, Gabriel Je, and Vergouwen, Mervyn DI

Published
2023

49. Glial cell response and microthrombosis in aneurysmal subarachnoid hemorrhage patients: An autopsy study

Author

Opleiding Neurologie, TN groep Hol, Biostatistiek Onderzoek, Other research (not in main researchprogram), Brain, Neurologen, Circulatory Health, Translational Neuroscience, Cancer, Koopman, Inez, Van Dijk, Bart J., Zuithoff, Nicolaas P.A., Sluijs, Jacqueline A., Van Der Kamp, Marije J., Baldew, Zelonna A.V., Frijns, Catharina J.M., Rinkel, Gabriel J.E., Hol, Elly M., Vergouwen, Mervyn D.I., Opleiding Neurologie, TN groep Hol, Biostatistiek Onderzoek, Other research (not in main researchprogram), Brain, Neurologen, Circulatory Health, Translational Neuroscience, Cancer, Koopman, Inez, Van Dijk, Bart J., Zuithoff, Nicolaas P.A., Sluijs, Jacqueline A., Van Der Kamp, Marije J., Baldew, Zelonna A.V., Frijns, Catharina J.M., Rinkel, Gabriel J.E., Hol, Elly M., and Vergouwen, Mervyn D.I.

Published
2023

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