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  1. Article: Chronic Unpredictable Stress Reduces Immunostaining for Connexins 43 and 30 and Myelin Basic Protein in the Rat Prelimbic and Orbitofrontal Cortices.

    Miguel-Hidalgo, José Javier / Moulana, Mohadetheh / Deloach, Preston Hardin / Rajkowska, Grazyna

    Chronic stress (Thousand Oaks, Calif.)

    2018  Volume 2

    Abstract: Background: Astrocytes and oligodendrocytes are pathologically altered in dorsolateral prefrontal and orbitofrontal cortices in major depressive disorder. In rat models of stress (major depressive disorder risk factor) astrocyte gap junction protein ... ...

    Abstract Background: Astrocytes and oligodendrocytes are pathologically altered in dorsolateral prefrontal and orbitofrontal cortices in major depressive disorder. In rat models of stress (major depressive disorder risk factor) astrocyte gap junction protein connexin 43 (Cx43) is reduced in the prelimbic cortex. Astrocyte connexins are recognized to strongly influence myelin maintenance in the central nervous system. However, it is unknown whether stress-related changes in Cx43 and the other major astrocyte connexin, Cx30, occur in the orbitofrontal cortex, or whether connexin changes are concurrent with disturbances in myelination.
    Methods: Frozen sections containing prelimbic cortex and orbitofrontal cortex of rats subjected to 35 days of chronic unpredictable stress and controls (n = 6/group) were immunolabeled for Cx43, Cx30, and myelin basic protein. Density of Cx43 or Cx30 immunoreactive puncta and area fraction of myelin basic protein immunoreactivity were measured in prelimbic cortex and orbitofrontal cortex and results analyzed with
    Results: Density of Cx43- and Cx30-positive puncta in both prelimbic cortex and orbitofrontal cortex was lower in chronic unpredictable stress-treated than in control rats. In both regions, the area fraction of myelin basic protein immunoreactivity was also lower in chronic unpredictable stress animals. Myelin basic protein area fraction was positively correlated with the density of Cx43-positive puncta in orbitofrontal cortex, and with Cx30 puncta in prelimbic cortex.
    Conclusion: Low Cx43 and Cx30 after chronic unpredictable stress in rat prelimbic cortex and orbitofrontal cortex suggests that reduced astrocytic gap junction density may generalize to the entire prefrontal cortex. Concurrent reduction of Cx43-, Cx30-, and myelin basic protein-immunolabeled structures is consistent with a mechanism linking changes in astrocyte gap junction proteins and disturbed myelin morphology in depression.
    Language English
    Publishing date 2018-12-04
    Publishing country United States
    Document type Journal Article
    ISSN 2470-5470
    ISSN 2470-5470
    DOI 10.1177/2470547018814186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Glucocorticoid-Induced Reductions of Myelination and Connexin 43 in Mixed Central Nervous System Cell Cultures Are Prevented by Mifepristone.

    Miguel-Hidalgo, José Javier / Carter, Kathleen / Deloach, Preston Hardin / Sanders, Leon / Pang, Yi

    Neuroscience

    2019  Volume 411, Page(s) 255–269

    Abstract: Repeated stress induces systemic elevations in glucocorticoid levels. Stress is also associated with alterations in central nervous system astrocytes and oligodendrocytes that involve connexins and myelin proteins. Corticosteroid elevation seems a major ... ...

    Abstract Repeated stress induces systemic elevations in glucocorticoid levels. Stress is also associated with alterations in central nervous system astrocytes and oligodendrocytes that involve connexins and myelin proteins. Corticosteroid elevation seems a major factor in stress-induced neuropathology. Changes in astrocyte connexins and myelin components may be important mediators for the neurological effects of corticosteroid elevations. Two primary cell culture models, myelination culture from rat embryonic spinal cord (SC) or cerebral cortex (CC) consisting of neurons and glial cells (oligodendrocytes, microglia and astrocytes), and mixed astrocyte-and-oligodendrocyte culture prepared from postnatal rat CC, were used in this study. Cell cultures were treated with either vehicle, corticosterone (CORT) with or without glucocorticoid receptor antagonist mifepristone, or dexamethasone (DEX) during the period of in vitro myelination. Immunoreactivity of astrocyte connexin 43 (Cx43) and oligodendrocyte myelin basic protein (MBP), or the myelination index (co-localization of MBP and phosphorylated neurofilament) was determined by double immunofluorescent labeling. Oligodendrocyte morphology was evaluated by Sholl analysis. Prolonged exposure to CORT or DEX induced dose-dependent reduction of the myelination index, and of immunostaining for MBP and Cx43 in SC and CC myelination cultures, which was prevented by mifepristone. In glial cultures single CORT or DEX exposure caused shrinkage and simplification of/' MBP- or CNPase-positive oligodendrocyte processes. The results support that concurrent effects of glucocorticoids on myelination and astrocyte Cx43 immunoreactivity are mediated by glucocorticoid receptors and may partially account for the involvement of CNS glia in the pathological effects of prolonged stress.
    MeSH term(s) Animals ; Cells, Cultured ; Cerebral Cortex/cytology ; Cerebral Cortex/drug effects ; Cerebral Cortex/metabolism ; Connexin 43/metabolism ; Dexamethasone/pharmacology ; Glucocorticoids/pharmacology ; Hormone Antagonists/pharmacology ; Mifepristone/pharmacology ; Myelin Sheath/drug effects ; Myelin Sheath/metabolism ; Neuroglia/cytology ; Neuroglia/drug effects ; Neuroglia/metabolism ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Rats ; Spinal Cord/cytology ; Spinal Cord/drug effects ; Spinal Cord/metabolism
    Chemical Substances Connexin 43 ; Glucocorticoids ; Hormone Antagonists ; Mifepristone (320T6RNW1F) ; Dexamethasone (7S5I7G3JQL)
    Language English
    Publishing date 2019-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 196739-3
    ISSN 1873-7544 ; 0306-4522
    ISSN (online) 1873-7544
    ISSN 0306-4522
    DOI 10.1016/j.neuroscience.2019.05.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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