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  1. Article ; Online: The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials.

    Rivera, Andrea D / Normanton, John R / Butt, Arthur M / Azim, Kasum

    International journal of molecular sciences

    2024  Volume 25, Issue 8

    Abstract: Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to a potential reduction in life expectancy by up to 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying ... ...

    Abstract Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to a potential reduction in life expectancy by up to 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying schizophrenia continue to remain enigmatic, with previous research yielding diverse and occasionally conflicting findings. Nonetheless, one consistently observed phenomenon in brain imaging studies of schizophrenia patients is the disruption of white matter, the bundles of myelinated axons that provide connectivity and rapid signalling between brain regions. Myelin is produced by specialised glial cells known as oligodendrocytes, which have been shown to be disrupted in post-mortem analyses of schizophrenia patients. Oligodendrocytes are generated throughout life by a major population of oligodendrocyte progenitor cells (OPC), which are essential for white matter health and plasticity. Notably, a decline in a specific subpopulation of OPC has been identified as a principal factor in oligodendrocyte disruption and white matter loss in the aging brain, suggesting this may also be a factor in schizophrenia. In this review, we analysed genomic databases to pinpoint intersections between aging and schizophrenia and identify shared mechanisms of white matter disruption and cognitive dysfunction.
    MeSH term(s) Humans ; Schizophrenia/metabolism ; Schizophrenia/pathology ; Schizophrenia/genetics ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; Aging/metabolism ; Animals ; Genomics/methods ; White Matter/metabolism ; White Matter/pathology ; Myelin Sheath/metabolism ; Brain/metabolism ; Brain/pathology
    Language English
    Publishing date 2024-04-18
    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/ijms25084452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Next generation drug connectivity mapping for acquiring therapeutic agents to differentially regulate myelination.

    Azim, Kasum / Rivera, Andrea Domenico / Butt, Arthur Morgan

    Neural regeneration research

    2022  Volume 18, Issue 4, Page(s) 797–798

    Language English
    Publishing date 2022-10-17
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.353486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Resolving the age-related decline in central nervous system myelin turnover and drug discovery for oligodendroglial rejuvenation.

    Rivera, Andrea Domenico / Butt, Arthur Morgan / Azim, Kasum

    Neural regeneration research

    2022  Volume 17, Issue 12, Page(s) 2677–2678

    Language English
    Publishing date 2022-05-16
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.338995
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Insights into ligand expression heterogeneity across multiple cell types in the adult forebrain that regulates neural stem cell behavior.

    Akkermann, Rainer / Azim, Kasum

    Neural regeneration research

    2019  Volume 14, Issue 8, Page(s) 1369–1371

    Language English
    Publishing date 2019-04-09
    Publishing country India
    Document type Journal Article
    ZDB-ID 2388460-5
    ISSN 1876-7958 ; 1673-5374
    ISSN (online) 1876-7958
    ISSN 1673-5374
    DOI 10.4103/1673-5374.251304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Targeting the Subventricular Zone to Promote Myelin Repair in the Aging Brain.

    Butt, Arthur Morgan / Rivera, Andrea Dominico / Fulton, Daniel / Azim, Kasum

    Cells

    2022  Volume 11, Issue 11

    Abstract: The subventricular zone (SVZ) is the largest and most active germinal zone in the adult forebrain. Neural stem cells (NSCs) of the SVZ generate olfactory interneurons throughout life and retain the intrinsic ability to generate oligodendrocytes (OLs), ... ...

    Abstract The subventricular zone (SVZ) is the largest and most active germinal zone in the adult forebrain. Neural stem cells (NSCs) of the SVZ generate olfactory interneurons throughout life and retain the intrinsic ability to generate oligodendrocytes (OLs), the myelinating cells of the central nervous system. OLs and myelin are targets in demyelinating diseases such as multiple sclerosis (MS). Remyelination is dependent on the ability of oligodendrocyte progenitor cells (OPCs) to proliferate, migrate, and terminally differentiate into myelinating OLs. During aging, there is a gradual decrease in the regenerative capacity of OPCs, and the consequent loss of OLs and myelin is a contributing factor in cognitive decline and the failure of remyelination in MS and other pathologies with aging contexts, including Alzheimer's disease (AD) and stroke. The age-related decrease in oligodendrogenesis has not been fully characterised but is known to reflect changes in intrinsic and environmental factors affecting the ability of OPCs to respond to pro-differentiation stimuli. Notably, SVZ-derived OPCs are an important source of remyelinating OLs in addition to parenchymal OPCs. In this mini-review, we briefly discuss differences between SVZ-derived and parenchymal OPCs in their responses to demyelination and highlight challenges associated with their study in vivo and how they can be targeted for regenerative therapies in the aged brain.
    MeSH term(s) Aged ; Brain/pathology ; Humans ; Lateral Ventricles ; Multiple Sclerosis/pathology ; Myelin Sheath/pathology ; Oligodendroglia
    Language English
    Publishing date 2022-05-31
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11111809
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.

    Rivera, Andrea D / Azim, Kasum / Macchi, Veronica / Porzionato, Andrea / Butt, Arthur M / De Caro, Raffaele

    Frontiers in cellular neuroscience

    2022  Volume 16, Page(s) 838007

    Abstract: Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) ...

    Abstract Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs)
    Language English
    Publishing date 2022-03-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2022.838007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Functional genomic analyses highlight a shift in Gpr17-regulated cellular processes in oligodendrocyte progenitor cells and underlying myelin dysregulation in the aged mouse cerebrum.

    Rivera, Andrea D / Pieropan, Francesca / Chacon-De-La-Rocha, Irene / Lecca, Davide / Abbracchio, Maria P / Azim, Kasum / Butt, Arthur M

    Aging cell

    2021  Volume 20, Issue 4, Page(s) e13335

    Abstract: Brain ageing is characterised by a decline in neuronal function and associated cognitive deficits. There is increasing evidence that myelin disruption is an important factor that contributes to the age-related loss of brain plasticity and repair ... ...

    Abstract Brain ageing is characterised by a decline in neuronal function and associated cognitive deficits. There is increasing evidence that myelin disruption is an important factor that contributes to the age-related loss of brain plasticity and repair responses. In the brain, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Currently, a leading hypothesis points to ageing as a major reason for the ultimate breakdown of remyelination in Multiple Sclerosis (MS). However, an incomplete understanding of the cellular and molecular processes underlying brain ageing hinders the development of regenerative strategies. Here, our combined systems biology and neurobiological approach demonstrate that oligodendroglial and myelin genes are amongst the most altered in the ageing mouse cerebrum. This was underscored by the identification of causal links between signalling pathways and their downstream transcriptional networks that define oligodendroglial disruption in ageing. The results highlighted that the G-protein coupled receptor Gpr17 is central to the disruption of OPCs in ageing and this was confirmed by genetic fate-mapping and cellular analyses. Finally, we used systems biology strategies to identify therapeutic agents that rejuvenate OPCs and restore myelination in age-related neuropathological contexts.
    MeSH term(s) Aging/genetics ; Aging/metabolism ; Animals ; Cell Differentiation/genetics ; Cerebrum/metabolism ; Genomics/methods ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelin Sheath/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism ; Oligodendrocyte Precursor Cells/metabolism ; RNA-Seq/methods ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/genetics ; Transcriptome/genetics
    Chemical Substances GPR17 protein, mouse ; Nerve Tissue Proteins ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2021-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13335
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6581: Show issues Location:
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  8. Article ; Online: Keeping the ageing brain wired: a role for purine signalling in regulating cellular metabolism in oligodendrocyte progenitors.

    Rivera, Andrea D / Chacon-De-La-Rocha, Irene / Pieropan, Francesca / Papanikolau, Maria / Azim, Kasum / Butt, Arthur M

    Pflugers Archiv : European journal of physiology

    2021  Volume 473, Issue 5, Page(s) 775–783

    Abstract: White matter (WM) is a highly prominent feature in the human cerebrum and is comprised of bundles of myelinated axons that form the connectome of the brain. Myelin is formed by oligodendrocytes and is essential for rapid neuronal electrical communication ...

    Abstract White matter (WM) is a highly prominent feature in the human cerebrum and is comprised of bundles of myelinated axons that form the connectome of the brain. Myelin is formed by oligodendrocytes and is essential for rapid neuronal electrical communication that underlies the massive computing power of the human brain. Oligodendrocytes are generated throughout life by oligodendrocyte precursor cells (OPCs), which are identified by expression of the chondroitin sulphate proteoglycan NG2 (Cspg4), and are often termed NG2-glia. Adult NG2+ OPCs are slowly proliferating cells that have the stem cell-like property of self-renewal and differentiation into a pool of 'late OPCs' or 'differentiation committed' OPCs(COPs) identified by specific expression of the G-protein-coupled receptor GPR17, which are capable of differentiation into myelinating oligodendrocytes. In the adult brain, these reservoirs of OPCs and COPs ensure rapid myelination of new neuronal connections formed in response to neuronal signalling, which underpins learning and cognitive function. However, there is an age-related decline in myelination that is associated with a loss of neuronal function and cognitive decline. The underlying causes of myelin loss in ageing are manifold, but a key factor is the decay in OPC 'stemness' and a decline in their replenishment of COPs, which results in the ultimate failure of myelin regeneration. These changes in ageing OPCs are underpinned by dysregulation of neuronal signalling and OPC metabolic function. Here, we highlight the role of purine signalling in regulating OPC self-renewal and the potential importance of GPR17 and the P2X7 receptor subtype in age-related changes in OPC metabolism. Moreover, age is the main factor in the failure of myelination in chronic multiple sclerosis and myelin loss in Alzheimer's disease, hence understanding the importance of purine signalling in OPC regeneration and myelination is critical for developing new strategies for promoting repair in age-dependent neuropathology.
    MeSH term(s) Aging/metabolism ; Animals ; Axons/metabolism ; Axons/physiology ; Brain/cytology ; Brain/growth & development ; Brain/metabolism ; Brain/physiology ; Humans ; Oligodendroglia/metabolism ; Oligodendroglia/physiology ; Purines/metabolism ; Signal Transduction
    Chemical Substances Purines
    Language English
    Publishing date 2021-03-13
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 6380-0
    ISSN 1432-2013 ; 0031-6768
    ISSN (online) 1432-2013
    ISSN 0031-6768
    DOI 10.1007/s00424-021-02544-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.35: Show issues Location:
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  9. Article: Mosaic Subventricular Origins of Forebrain Oligodendrogenesis.

    Azim, Kasum / Berninger, Benedikt / Raineteau, Olivier

    Frontiers in neuroscience

    2016  Volume 10, Page(s) 107

    Abstract: In the perinatal as well as the adult CNS, the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates neurons and oligodendrocytes (OLs), the myelin forming cells of the CNS. Recent ... ...

    Abstract In the perinatal as well as the adult CNS, the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates neurons and oligodendrocytes (OLs), the myelin forming cells of the CNS. Recent advances in the field are beginning to shed light regarding SVZ heterogeneity, with the existence of spatially segregated microdomains that are intrinsically biased to generate phenotypically distinct neuronal populations. Although most research has focused on this regionalization in the context of neurogenesis, newer findings underline that this also applies for the genesis of OLs under the control of specific patterning molecules. In this mini review, we discuss the origins as well as the mechanisms that induce and maintain SVZ regionalization. These come in the flavor of specific signaling ligands and subsequent initiation of transcriptional networks that provide a basis for subdividing the SVZ into distinct lineage-specific microdomains. We further emphasize canonical Wnts and FGF2 as essential signaling pathways for the regional genesis of OL progenitors from NSCs of the dorsal SVZ. This aspect of NSC biology, which has so far received little attention, may unveil new avenues for appropriately recruiting NSCs in demyelinating diseases.
    Language English
    Publishing date 2016-03-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2016.00107
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  10. Article ; Online: Myelin repair is fostered by the corticosteroid medrysone specifically acting on astroglial subpopulations.

    Silva Oliveira Junior, Markley / Schira-Heinen, Jessica / Reiche, Laura / Han, Seulki / de Amorim, Vanessa Cristina Meira / Lewen, Isabel / Gruchot, Joel / Göttle, Peter / Akkermann, Rainer / Azim, Kasum / Küry, Patrick

    EBioMedicine

    2022  Volume 83, Page(s) 104204

    Abstract: Background: Multiple sclerosis is characterised by inflammation, oligodendrocyte loss and axonal demyelination and shows an additional impact on astrocytes, and their polarization. Although a certain degree of spontaneous myelin repair can be observed, ... ...

    Abstract Background: Multiple sclerosis is characterised by inflammation, oligodendrocyte loss and axonal demyelination and shows an additional impact on astrocytes, and their polarization. Although a certain degree of spontaneous myelin repair can be observed, disease progression, and aging impair regeneration efforts highlighting the need to better understand glial cell dynamics to establish specific regenerative treatments.
    Methods: Applying a chronic demyelination model, we here analysed demyelination and remyelination related effects on astrocytes and stem cell niches and studied the consequences of medrysone application on myelin repair, and astrocyte polarization.
    Findings: Medrysone induced recovery of mature oligodendrocytes, myelin expression and node formation. In addition, C3d/S100a10 co-expression in astrocytes was enhanced. Moreover, Timp1 expression in C3d positive astrocytes revealed another astrocytic phenotype with a myelination promoting character.
    Interpretation: Based on these findings, specific astrocyte subpopulations are suggested to act in a myelin regenerative way and manner the regulation of which can be positively modulated by this corticosteroid.
    Funding: This work was supported by the Jürgen Manchot Stiftung, the Research Commission of the medical faculty of the Heinrich-Heine-University of Düsseldorf, the Christiane and Claudia Hempel Foundation for clinical stem cell research and the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung.
    MeSH term(s) Adrenal Cortex Hormones ; Animals ; Astrocytes/metabolism ; Cuprizone/metabolism ; Cuprizone/pharmacology ; Demyelinating Diseases/metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism ; Oligodendroglia/metabolism ; Pregnenediones
    Chemical Substances Adrenal Cortex Hormones ; Pregnenediones ; Cuprizone (5N16U7E0AO) ; medrysone (D2UFC189XF)
    Language English
    Publishing date 2022-08-08
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104204
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7090: Show issues Location:
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