Artikel ; Online: Deficient mitochondrial respiration in astrocytes impairs trace fear conditioning and increases naloxone-precipitated aversion in morphine-dependent mice.
2022 Band 70, Heft 7, Seite(n) 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-Begriff(e) | 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 |
| Chemische Substanzen | Membrane Proteins ; Narcotic Antagonists ; Naloxone (36B82AMQ7N) ; Morphine (76I7G6D29C) ; Alkyl and Aryl Transferases (EC 2.5.-) ; COX10 protein, mouse (EC 2.5.1.-) |
| Sprache | Englisch |
| Erscheinungsdatum | 2022-03-11 |
| Erscheinungsland | United States |
| Dokumenttyp | 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 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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