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

First Author  Murlanova K Year  2022
Journal  Glia Volume  70
Issue  7 Pages  1289-1300
PubMed ID  35275429 Mgi Jnum  J:325458
Mgi Id  MGI:7278908 Doi  10.1002/glia.24169
Citation  Murlanova K, et al. (2022) Deficient mitochondrial respiration in astrocytes impairs trace fear conditioning and increases naloxone-precipitated aversion in morphine-dependent mice. Glia 70(7):1289-1300
abstractText  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.
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