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  1. Article ; Online: Deficient mitochondrial respiration in astrocytes impairs trace fear conditioning and increases naloxone-precipitated aversion in morphine-dependent mice.

    Murlanova, Kateryna / Jouroukhin, Yan / Huseynov, Shovgi / Pletnikova, Olga / Morales, Michael J / Guan, Yun / Baraban, Jay M / Bergles, Dwight E / Pletnikov, Mikhail V

    Glia

    2022  Volume 70, Issue 7, Page(s) 1289–1300

    Abstract: Mitochondria are abundant in the fine processes of astrocytes, however, potential roles for astrocyte mitochondria remain poorly understood. In the present study, we performed a systematic examination of the effects of abnormal oxidative phosphorylation ... ...

    Abstract Mitochondria are abundant in the fine processes of astrocytes, however, potential roles for astrocyte mitochondria remain poorly understood. In the present study, we performed a systematic examination of the effects of abnormal oxidative phosphorylation in astrocytes on several mouse behaviors. Impaired astrocyte oxidative phosphorylation was produced by astrocyte-specific deletion of the nuclear mitochondrial gene, Cox10, that encodes an accessory protein of complex IV, the protoheme:heme-O-farnesyl transferase. As expected, conditional deletion of the Cox10 gene in mice (cKO mice) significantly reduced expression of COX10 and Cytochrome c oxidase subunit I (MTCO1) of Complex IV, resulting in decreased oxidative phosphorylation without significantly affecting glycolysis. No effects of the deletion were observed on locomotor activity, anxiety-like behavior, nociception, or spontaneous alternation. Cox10 cKO female mice exhibited mildly impaired novel object recognition, while Cox10 cKO male mice were moderately deficient in trace fear conditioning. No group-related changes were observed in conditional place preference (CPP) that assessed effects of morphine on reward. In contrast to CPP, Cox10 cKO mice demonstrated significantly increased aversive behaviors produced by naloxone-precipitated withdrawal following chronic exposure to morphine, that is, jumping and avoidance behavior as assessed by conditional place aversion (CPA). Our study suggests that astrocyte oxidative phosphorylation may contribute to behaviors associated with greater cognitive load and/or aversive and stressful conditions.
    MeSH term(s) Alkyl and Aryl Transferases/metabolism ; Animals ; Astrocytes/metabolism ; Fear ; Female ; Male ; Membrane Proteins/metabolism ; Mice ; Mitochondria/metabolism ; Morphine/metabolism ; Morphine/pharmacology ; Morphine Dependence/metabolism ; Morphine Dependence/psychology ; Naloxone/metabolism ; Naloxone/pharmacology ; Narcotic Antagonists/metabolism ; Narcotic Antagonists/pharmacology ; Respiration ; Substance Withdrawal Syndrome/metabolism ; Substance Withdrawal Syndrome/psychology
    Chemical Substances Membrane Proteins ; Narcotic Antagonists ; Naloxone (36B82AMQ7N) ; Morphine (76I7G6D29C) ; Alkyl and Aryl Transferases (EC 2.5.-) ; COX10 protein, mouse (EC 2.5.1.-)
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.24169
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Loss of Astrocytic µ Opioid Receptors Exacerbates Aversion Associated with Morphine Withdrawal in Mice: Role of Mitochondrial Respiration.

    Murlanova, Kateryna / Jouroukhin, Yan / Novototskaya-Vlasova, Ksenia / Huseynov, Shovgi / Pletnikova, Olga / Morales, Michael J / Guan, Yun / Kamiya, Atsushi / Bergles, Dwight E / Dietz, David M / Pletnikov, Mikhail V

    Cells

    2023  Volume 12, Issue 10

    Abstract: Astrocytes express mu/µ opioid receptors, but the function of these receptors remains poorly understood. We evaluated the effects of astrocyte-restricted knockout of µ opioid receptors on reward- and aversion-associated behaviors in mice chronically ... ...

    Abstract Astrocytes express mu/µ opioid receptors, but the function of these receptors remains poorly understood. We evaluated the effects of astrocyte-restricted knockout of µ opioid receptors on reward- and aversion-associated behaviors in mice chronically exposed to morphine. Specifically, one of the floxed alleles of the
    MeSH term(s) Mice ; Animals ; Morphine/adverse effects ; Astrocytes ; Receptors, Opioid ; Narcotic Antagonists/pharmacology ; Naloxone/pharmacology ; Mice, Knockout ; Receptors, Opioid, mu/genetics
    Chemical Substances Morphine (76I7G6D29C) ; Receptors, Opioid ; Narcotic Antagonists ; Naloxone (36B82AMQ7N) ; Receptors, Opioid, mu
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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/cells12101412
    Database MEDical Literature Analysis and Retrieval System OnLINE

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