Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state

We investigated the changes in redox state and protein expression in selected parts of the rat brain induced by a 4 week administration of morphine (10 mg/kg/day). We found a significant reduction in lipid peroxidation that mostly persisted for 1 week after morphine withdrawal. Morphine treatment le...

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Main Authors: Hejnova Lucie, Hronova Anna, Drastichova Zdenka, Novotny Jiri
Format: Article
Language:English
Published: De Gruyter 2024-04-01
Series:Open Life Sciences
Subjects:
Online Access:https://doi.org/10.1515/biol-2022-0858
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author Hejnova Lucie
Hronova Anna
Drastichova Zdenka
Novotny Jiri
author_facet Hejnova Lucie
Hronova Anna
Drastichova Zdenka
Novotny Jiri
author_sort Hejnova Lucie
collection DOAJ
description We investigated the changes in redox state and protein expression in selected parts of the rat brain induced by a 4 week administration of morphine (10 mg/kg/day). We found a significant reduction in lipid peroxidation that mostly persisted for 1 week after morphine withdrawal. Morphine treatment led to a significant increase in complex II in the cerebral cortex (Crt), which was accompanied by increased protein carbonylation, in contrast to the other brain regions studied. Glutathione levels were altered differently in the different brain regions after morphine treatment. Using label-free quantitative proteomic analysis, we found some specific changes in protein expression profiles in the Crt, hippocampus, striatum, and cerebellum on the day after morphine withdrawal and 1 week later. A common feature was the upregulation of anti-apoptotic proteins and dysregulation of the extracellular matrix. Our results indicate that the tested protocol of morphine administration has no significant toxic effect on the rat brain. On the contrary, it led to a decrease in lipid peroxidation and activation of anti-apoptotic proteins. Furthermore, our data suggest that long-term treatment with morphine acts specifically on different brain regions and that a 1 week drug withdrawal is not sufficient to normalize cellular redox state and protein levels.
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spelling doaj.art-2acfeb067a1d49e6ac56e969ad6052452024-04-22T19:39:30ZengDe GruyterOpen Life Sciences2391-54122024-04-011915617010.1515/biol-2022-0858Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox stateHejnova Lucie0Hronova Anna1Drastichova Zdenka2Novotny Jiri3Department of Physiology, Faculty of Science, Charles University, Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, Prague, Czech RepublicWe investigated the changes in redox state and protein expression in selected parts of the rat brain induced by a 4 week administration of morphine (10 mg/kg/day). We found a significant reduction in lipid peroxidation that mostly persisted for 1 week after morphine withdrawal. Morphine treatment led to a significant increase in complex II in the cerebral cortex (Crt), which was accompanied by increased protein carbonylation, in contrast to the other brain regions studied. Glutathione levels were altered differently in the different brain regions after morphine treatment. Using label-free quantitative proteomic analysis, we found some specific changes in protein expression profiles in the Crt, hippocampus, striatum, and cerebellum on the day after morphine withdrawal and 1 week later. A common feature was the upregulation of anti-apoptotic proteins and dysregulation of the extracellular matrix. Our results indicate that the tested protocol of morphine administration has no significant toxic effect on the rat brain. On the contrary, it led to a decrease in lipid peroxidation and activation of anti-apoptotic proteins. Furthermore, our data suggest that long-term treatment with morphine acts specifically on different brain regions and that a 1 week drug withdrawal is not sufficient to normalize cellular redox state and protein levels.https://doi.org/10.1515/biol-2022-0858morphinewithdrawalbrainoxidative stressproteomics
spellingShingle Hejnova Lucie
Hronova Anna
Drastichova Zdenka
Novotny Jiri
Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
Open Life Sciences
morphine
withdrawal
brain
oxidative stress
proteomics
title Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
title_full Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
title_fullStr Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
title_full_unstemmed Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
title_short Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
title_sort long term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
topic morphine
withdrawal
brain
oxidative stress
proteomics
url https://doi.org/10.1515/biol-2022-0858
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AT drastichovazdenka longtermadministrationofmorphinespecificallyaltersthelevelofproteinexpressionindifferentbrainregionsandaffectstheredoxstate
AT novotnyjiri longtermadministrationofmorphinespecificallyaltersthelevelofproteinexpressionindifferentbrainregionsandaffectstheredoxstate