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  1. Article ; Online: Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis.

    López-Muguruza, Eneritz / Matute, Carlos

    International journal of molecular sciences

    2023  Volume 24, Issue 16

    Abstract: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play a vital role in maintaining the integrity of myelin, the protective sheath around ... ...

    Abstract Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play a vital role in maintaining the integrity of myelin, the protective sheath around nerve fibres essential for efficient signal transmission. However, in MS, oligodendrocytes become dysfunctional, leading to myelin damage and axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction and alterations in glucose and lipid metabolism, contribute significantly to the pathogenesis of MS. Mitochondrial dysfunction is observed in both immune cells and oligodendrocytes within the CNS of MS patients. Impaired mitochondrial function leads to energy deficits, affecting crucial processes such as impulse transmission and axonal transport, ultimately contributing to neurodegeneration. Moreover, mitochondrial dysfunction is linked to the generation of reactive oxygen species (ROS), exacerbating myelin damage and inflammation. Altered glucose metabolism affects the energy supply required for oligodendrocyte function and myelin synthesis. Dysregulated lipid metabolism results in changes to the composition of myelin, affecting its stability and integrity. Importantly, low levels of polyunsaturated fatty acids in MS are associated with upregulated lipid metabolism and enhanced glucose catabolism. Understanding the intricate relationship between these mechanisms is crucial for developing targeted therapies to preserve myelin and promote neurological recovery in individuals with MS. Addressing these metabolic aspects may offer new insights into potential therapeutic strategies to halt disease progression and improve the quality of life for MS patients.
    MeSH term(s) Humans ; Myelin Sheath ; Multiple Sclerosis ; Quality of Life ; Oligodendroglia ; Energy Metabolism ; Glucose
    Chemical Substances Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-08-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241612912
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  2. Article ; Online: A nonlinear meccano for Alzheimer's emergence by amyloid β-mediated glutamatergic hyperactivity.

    Bonifazi, Giulio / Luchena, Celia / Gaminde-Blasco, Adhara / Ortiz-Sanz, Carolina / Capetillo-Zarate, Estibaliz / Matute, Carlos / Alberdi, Elena / De Pittà, Maurizio

    Neurobiology of disease

    2024  Volume 194, Page(s) 106473

    Abstract: The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its ... ...

    Abstract The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-β (Aβ) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate Aβ accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing Aβ-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to the emergence of various modes of hyperactivity. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.
    MeSH term(s) Humans ; Amyloid beta-Peptides ; Alzheimer Disease ; Neurons/physiology ; Cell Communication
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2024.106473
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    Zs.A 4444: Show issues Location:
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  3. Article ; Online: Excitotoxicity therapy for stroke patients still alive.

    Domercq, Maria / Matute, Carlos

    EBioMedicine

    2018  Volume 39, Page(s) 3–4

    MeSH term(s) Animals ; Disease Management ; Gene Expression ; Genetic Therapy ; Mesenchymal Stem Cell Transplantation ; Stroke/etiology ; Stroke/metabolism ; Stroke/therapy ; Transgenes ; Treatment Outcome
    Language English
    Publishing date 2018-12-20
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2018.12.027
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  4. Article ; Online: Glutamate receptors and white matter stroke.

    Fern, Robert / Matute, Carlos

    Neuroscience letters

    2018  Volume 694, Page(s) 86–92

    Abstract: White matter (WM) damage during ischemia occurs at multiple sites including myelin, oligodendrocytes, astrocytes and axons. A major driver of WM demise is excitoxicity as a consequence of excessive glutamate release by vesicular and non-vesicular ... ...

    Abstract White matter (WM) damage during ischemia occurs at multiple sites including myelin, oligodendrocytes, astrocytes and axons. A major driver of WM demise is excitoxicity as a consequence of excessive glutamate release by vesicular and non-vesicular mechanisms from axons and glial cells. This results in over-activation of ionotropic glutamate receptors (GluRs) profusely expressed by all cell compartments in WM. Thus, blocking excitotoxicity in WM with selective antagonists of those receptors has a potential therapeutic value. The significance of WM GluR expression for WM stroke injury is the focus of this review, and we will examine the role of GluRs in injury to myelin, oligodendrocytes, astrocytes and the axon cylinder.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Axons/metabolism ; Brain Ischemia/complications ; Brain Ischemia/metabolism ; Glutamic Acid/metabolism ; Homeostasis ; Humans ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; Receptors, Glutamate/metabolism ; Stroke/complications ; Stroke/metabolism ; White Matter/metabolism ; White Matter/pathology
    Chemical Substances Receptors, Glutamate ; Glutamic Acid (3KX376GY7L)
    Language English
    Publishing date 2018-11-23
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2018.11.031
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    Zs.A 1166: Show issues Location:
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  5. Article: Functional and Metabolic Characterization of Microglia Culture in a Defined Medium.

    Montilla, Alejandro / Zabala, Alazne / Matute, Carlos / Domercq, María

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 22

    Abstract: Microglia are the endogenous immune cells of the brain and act as sensor of infection and pathologic injury to the brain, leading to a rapid plastic process of activation that culminates in the endocytosis and phagocytosis of damaged tissue. Microglia ... ...

    Abstract Microglia are the endogenous immune cells of the brain and act as sensor of infection and pathologic injury to the brain, leading to a rapid plastic process of activation that culminates in the endocytosis and phagocytosis of damaged tissue. Microglia cells are the most plastic cells in the brain. Microglia isolation from their environment as well as culturing them in the presence of serum alter their function and lead to a rapid loss of their signature gene expression. Previous studies have identified pivotal factors allowing microglia culture in the absence of serum. Here, we have further characterized the function, expression of markers, metabolic status and response to pro and anti-inflammatory stimulus of microglia isolated by magnetic-activated cell sorting and cultured in a chemically defined medium. We have compared this new method with previous traditional protocols of culturing microglia that use high concentrations of serum.
    Language English
    Publishing date 2020-02-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.00022
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  6. Article ; Online: Glutamate and ATP signalling in white matter pathology.

    Matute, Carlos

    Journal of anatomy

    2011  Volume 219, Issue 1, Page(s) 53–64

    Abstract: Excessive signalling by excitatory neurotransmitters like glutamate and ATP can be deleterious to neurons and oligodendroglia, and cause disease. In particular, sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate ... ...

    Abstract Excessive signalling by excitatory neurotransmitters like glutamate and ATP can be deleterious to neurons and oligodendroglia, and cause disease. In particular, sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-d-aspartate (NMDA) receptors damages oligodendrocytes, a feature that depends entirely on Ca(2+) overload of the cytoplasm and that can be initiated by disruption of glutamate homeostasis. Thus, inhibition of glutamate uptake by activated microglia can compromise glutamate homeostasis and induce oligodendrocyte excitotoxicity. Moreover, non-lethal, brief activation of kainate receptors in oligodendrocytes rapidly sensitizes these cells to complement attack as a consequence of oxidative stress. In addition to glutamate, ATP signalling can directly trigger oligodendrocyte excitotoxicity via activation of Ca(2+) -permeable P2X7 purinergic receptors, which mediates ischaemic damage to white matter (WM) and causes lesions that are reminiscent of multiple sclerosis (MS) plaques. Conversely, blockade of P2X7 receptors attenuates post-ischaemic injury to WM and ameliorates chronic experimental autoimmune encephalomyelitis, a model of MS. Importantly, P2X7 expression is elevated in normal-appearing WM in patients with MS, suggesting that signalling through this receptor in oligodendrocytes may be enhanced in this disease. Altogether, these observations reveal novel mechanisms by which altered glutamate and ATP homeostasis can trigger oligodendrocyte death. This review aims at summarizing current knowledge about the mechanisms leading to WM damage as a consequence of altered neurotransmitter signalling, and their relevance to disease. This knowledge will generate new therapeutic avenues to treat more efficiently acute and chronic WM pathology.
    MeSH term(s) Adenosine Triphosphate/metabolism ; Brain/pathology ; Brain Ischemia/physiopathology ; Cell Death/physiology ; Glutamic Acid/metabolism ; Humans ; Oligodendroglia/physiology ; Signal Transduction/physiology
    Chemical Substances Glutamic Acid (3KX376GY7L) ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2011-01-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2955-5
    ISSN 1469-7580 ; 0021-8782
    ISSN (online) 1469-7580
    ISSN 0021-8782
    DOI 10.1111/j.1469-7580.2010.01339.x
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  7. Article: Cannabinoid CB

    Manterola, Andrea / Chara, Juan Carlos / Aguado, Tania / Palazuelos, Javier / Matute, Carlos / Mato, Susana

    Frontiers in neuroanatomy

    2022  Volume 16, Page(s) 1030060

    Abstract: Adult oligodendrocyte progenitor cells (OPCs) give rise to myelinating oligodendrocytes through life and play crucial roles in brain homeostasis and plasticity during health and disease. Cannabinoid compounds acting through ... ...

    Abstract Adult oligodendrocyte progenitor cells (OPCs) give rise to myelinating oligodendrocytes through life and play crucial roles in brain homeostasis and plasticity during health and disease. Cannabinoid compounds acting through CB
    Language English
    Publishing date 2022-10-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452969-2
    ISSN 1662-5129
    ISSN 1662-5129
    DOI 10.3389/fnana.2022.1030060
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  8. Article: A Neuron, Microglia, and Astrocyte Triple Co-culture Model to Study Alzheimer's Disease.

    Luchena, Celia / Zuazo-Ibarra, Jone / Valero, Jorge / Matute, Carlos / Alberdi, Elena / Capetillo-Zarate, Estibaliz

    Frontiers in aging neuroscience

    2022  Volume 14, Page(s) 844534

    Abstract: Glial cells are essential to understand Alzheimer's disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and ... ...

    Abstract Glial cells are essential to understand Alzheimer's disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and glia communication. Currently available models such as co-cultures require complex methodologies and/or might not be affordable for all laboratories. With this in mind, we aimed to establish a straightforward
    Language English
    Publishing date 2022-04-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2022.844534
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  9. Article ; Online: Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells.

    Bernal-Chico, Ana / Tepavcevic, Vanja / Manterola, Andrea / Utrilla, Carmen / Matute, Carlos / Mato, Susana

    Glia

    2022  Volume 71, Issue 1, Page(s) 103–126

    Abstract: The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid ... ...

    Abstract The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ
    MeSH term(s) Animals ; Humans ; Endocannabinoids ; Cannabinoids/pharmacology ; Receptors, Cannabinoid/physiology ; Dronabinol ; Brain Diseases ; Microglia
    Chemical Substances Endocannabinoids ; Cannabinoids ; Receptors, Cannabinoid ; Dronabinol (7J8897W37S)
    Language English
    Publishing date 2022-03-30
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.24172
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    Zs.A 2345: Show issues Location:
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  10. Article ; Online: Calcium dyshomeostasis in white matter pathology.

    Matute, Carlos

    Cell calcium

    2010  Volume 47, Issue 2, Page(s) 150–157

    Abstract: Calcium (Ca2+) dyshomeostasis is a major event in the pathophysiology of white matter disorders of the brain and spinal cord. All cellular components of white matter, including macroglial cells and axons, are endowed with membrane Ca2+-permeable ... ...

    Abstract Calcium (Ca2+) dyshomeostasis is a major event in the pathophysiology of white matter disorders of the brain and spinal cord. All cellular components of white matter, including macroglial cells and axons, are endowed with membrane Ca2+-permeable receptors and channels lodged in the cell membrane, as well as store-operated channels and pumps. Intracellular Ca2+ overload resulting from deregulated activity of channels, such as those opened by glutamate and ATP, is deleterious to glia and axons. In this review, I summarize recent advances in our understanding of white matter Ca2+ dyshomeostasis in experimental paradigms which are relevant to stroke, perinatal ischemia, multiple sclerosis, psychiatric disorders, Alzheimer's disease and traumatic injury, and discuss some of the clinical implications of these findings.
    MeSH term(s) Animals ; Axons/metabolism ; Axons/pathology ; Brain Diseases/metabolism ; Brain Diseases/pathology ; Brain Diseases/physiopathology ; Calcium/metabolism ; Calcium Channels/metabolism ; Calcium Signaling ; Cell Death ; Homeostasis ; Humans ; Neuroglia/metabolism ; Neuroglia/pathology ; Reactive Oxygen Species/metabolism ; Spinal Cord Diseases/metabolism ; Spinal Cord Diseases/pathology ; Spinal Cord Diseases/physiopathology
    Chemical Substances Calcium Channels ; Reactive Oxygen Species ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2010-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2009.12.004
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