Alterations in the Proteome and Phosphoproteome Profiles of Rat Hippocampus after Six Months of Morphine Withdrawal: Comparison with the Forebrain Cortex

Ujcikova, Hana; Eckhardt, Adam; Hejnova, Lucie; Novotný, Jiřı́; Svoboda, Petr

doi:10.3390/biomedicines10010080

Cited by 6 publications

(4 citation statements)

References 56 publications

(88 reference statements)

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“…Among upregulated proteins, four of these were associated with the change in energy metabolism: electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial ( Etfdh , ↑2.6-fold), ATPase inhibitor, mitochondrial ( Atpif ,↑2.4-fold), complex I-B17 ( Ndufb6 , ↑2.4-fold), and cytochrome c oxidase subunit 2 ( Mtco2 , ↑2.3-fold). We previously reported that the majority of altered hippocampal proteins were related to energy metabolism after both chronic morphine treatment (10–50 mg/kg, 10 days) and subsequent drug withdrawal (3 weeks, 3 months, 6 months) [ 14 , 15 , 16 ]. Volcano plots representing significantly altered proteins identified in rat hippocampus after treatment with 3 mg/kg of morphine, LYS739 , and LYS744 are depicted in Figure 2 C. Hierarchical heatmap clustering of all identified protein expression profiles in rat hippocampus is presented in Figure 3 .…”

Section: Resultsmentioning

confidence: 99%

“…Rat brain cortex and hippocampus were selected as a part of the central nervous system; rat spleen lymphocytes represented the peripheral region. Our previous data showed the opposite effect of morphine treatment and withdrawal on proteome changes in cortical and hippocampal samples [ 13 , 14 , 15 , 16 ]. Label-free quantification (MaxLFQ) was used for all proteomic analyses [ 13 , 14 , 15 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus; Comparison with Changes Induced by Morphine

et al. 2022

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This work aimed to test the effect of 7-day exposure of rats to multifunctional enkephalin analogs LYS739 and LYS744 at doses of 3 mg/kg and 10 mg/kg on the protein composition of rat spleen lymphocytes, brain cortex, and hippocampus. Alterations of proteome induced by LYS739 and LYS744 were compared with those elicited by morphine. The changes in rat proteome profiles were analyzed by label-free quantification (MaxLFQ). Proteomic analysis indicated that the treatment with 3 mg/kg of LYS744 caused significant alterations in protein expression levels in spleen lymphocytes (45), rat brain cortex (31), and hippocampus (42). The identified proteins were primarily involved in RNA processing and the regulation of cytoskeletal dynamics. In spleen lymphocytes, the administration of the higher 10 mg/kg dose of both enkephalin analogs caused major, extensive modifications in protein expression levels: LYS739 (119) and LYS744 (182). Among these changes, the number of proteins associated with immune responses and apoptotic processes was increased. LYS739 treatment resulted in the highest number of alterations in the rat brain cortex (152) and hippocampus (45). The altered proteins were functionally related to the regulation of transcription and cytoskeletal reorganization, which plays an essential role in neuronal plasticity. Administration with LYS744 did not increase the number of altered proteins in the brain cortex (26) and hippocampus (26). Our findings demonstrate that the effect of κ-OR full antagonism of LYS744 is opposite in the central nervous system and the peripheral region (spleen lymphocytes).

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus; Comparison with Changes Induced by Morphine

et al. 2022

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“…The DEPs were assessed for protein–protein interaction (PPI) analysis using STRING (11.0) web server. , The PPI network was performed at a high confidence level of 0.700 allowing all active interaction sources including direct (physical) and indirect (functional) associations. The evidence of these predicted interactions is presented via genomic context, coexpression, prior knowledge, and high-throughput experiments.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the Proteomic Landscape of Mycobacterium tuberculosis in Response to Acid and Oxidative Stresses

et al. 2022

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The fundamental to the pathogenicity of Mycobacterium tuberculosis (Mtb) is the modulation in the control mechanisms that play a role in sensing and counteracting the microbicidal milieu encompassing various cellular stresses inside the human host. To understand such changes, we measured the cellular proteome of Mtb subjected to different stresses using a quantitative proteomics approach. We identified defined sets of Mtb proteins that are modulated in response to acid and a sublethal dose of diamide and H 2 O 2 treatments. Notably, proteins involved in metabolic, catalytic, and binding functions are primarily affected under these stresses. Moreover, our analysis led to the observations that during acidic stress Mtb enters into energy-saving mode simultaneously modulating the acid tolerance system, whereas under diamide and H 2 O 2 stresses, there were prominent changes in the biosynthesis and homeostasis pathways, primarily modifying the resistance mechanism in diamide-treated bacteria while causing metabolic arrest in H 2 O 2 -treated bacilli. Overall, we delineated the adaptive mechanisms that Mtb may utilize under physiological stresses and possible overlap between the responses to these stress conditions. In addition to offering important protein signatures that can be exploited for future mechanistic studies, our study highlights the importance of proteomics in understanding complex adjustments made by the human pathogen during infection.

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“…An overactive incentive-motivational system centered in ventral tegmental area ( VTA ) dopamine ( DA ) neurons and its neural projections to the nucleus accumbens ( NAc ) serves as the “accelerator” (reward, persistent drug-induced behaviors) ( Figure 1 ). Subregions of the prefrontal cortex ( PFC ) play both direct and subtle regulatory roles as a “behavioral brake” over drug use (inhibitory control, executive function) and is vulnerable to disruption by chronic opioid exposure leading to heightened preoccupation and anticipation of drug acquisition ( Ujcikova et al, 2021 ; Ceceli et al, 2023 ). A well-characterized role for the 5-HT 2A R in meso-corticolimbic neurocircuitry serves to illustrate the power and complexity of this system ( Figure 1 ).…”

Section: The 5-ht 2a R As a Target For Opioid Use ...mentioning

confidence: 99%

μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges

Salinsky,

Merritt,

Zamora

et al. 2023

Front. Pharmacol.

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Opioid misuse and opioid-involved overdose deaths are a massive public health problem involving the intertwined misuse of prescription opioids for pain management with the emergence of extremely potent fentanyl derivatives, sold as standalone products or adulterants in counterfeit prescription opioids or heroin. The incidence of repeated opioid overdose events indicates a problematic use pattern consistent with the development of the medical condition of opioid use disorder (OUD). Prescription and illicit opioids reduce pain perception by activating µ-opioid receptors (MOR) localized to the central nervous system (CNS). Dysregulation of meso-corticolimbic circuitry that subserves reward and adaptive behaviors is fundamentally involved in the progressive behavioral changes that promote and are consequent to OUD. Although opioid-induced analgesia and the rewarding effects of abused opioids are primarily mediated through MOR activation, serotonin (5-HT) is an important contributor to the pharmacology of opioid abused drugs (including heroin and prescription opioids) and OUD. There is a recent resurgence of interest into psychedelic compounds that act primarily through the 5-HT2A receptor (5-HT2AR) as a new frontier in combatting such diseases (e.g., depression, anxiety, and substance use disorders). Emerging data suggest that the MOR and 5-HT2AR crosstalk at the cellular level and within key nodes of OUD circuitry, highlighting a major opportunity for novel pharmacological intervention for OUD. There is an important gap in the preclinical profiling of psychedelic 5-HT2AR agonists in OUD models. Further, as these molecules carry risks, additional analyses of the profiles of non-hallucinogenic 5-HT2AR agonists and/or 5-HT2AR positive allosteric modulators may provide a new pathway for 5-HT2AR therapeutics. In this review, we discuss the opportunities and challenges associated with utilizing 5-HT2AR agonists as therapeutics for OUD.

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Alterations in the Proteome and Phosphoproteome Profiles of Rat Hippocampus after Six Months of Morphine Withdrawal: Comparison with the Forebrain Cortex

Cited by 6 publications

References 56 publications

The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus; Comparison with Changes Induced by Morphine

The Dose-Dependent Effects of Multifunctional Enkephalin Analogs on the Protein Composition of Rat Spleen Lymphocytes, Cortex, and Hippocampus; Comparison with Changes Induced by Morphine

Deciphering the Proteomic Landscape of Mycobacterium tuberculosis in Response to Acid and Oxidative Stresses

μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges

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