Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine
Drug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have no...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/11/7/683 |
| _version_ | 1797526697069772800 |
|---|---|
| author | Zdenka Drastichova Lucie Hejnova Radka Moravcova Jiri Novotny |
| author_facet | Zdenka Drastichova Lucie Hejnova Radka Moravcova Jiri Novotny |
| author_sort | Zdenka Drastichova |
| collection | DOAJ |
| description | Drug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have not yet been fully identified. In the present study, changes in proteomic and phosphoproteomic profiles of selected brain regions (cortex, hippocampus, striatum, and cerebellum) from rats abstaining for six months after cessation of chronic treatment with morphine were determined by label-free quantitative (LFQ) proteomic analysis. Interestingly, prolonged morphine withdrawal was found to be associated especially with alterations in protein phosphorylation and to a lesser extent in protein expression. Gene ontology (GO) term analysis revealed enrichment in biological processes related to synaptic plasticity, cytoskeleton organization, and GTPase activity. More specifically, significant changes were observed in proteins localized in synaptic vesicles (e.g., synapsin-1, SV2a, Rab3a), in the active zone of the presynaptic nerve terminal (e.g., Bassoon, Piccolo, Rims1), and in the postsynaptic density (e.g., cadherin 13, catenins, Arhgap35, Shank3, Arhgef7). Other differentially phosphorylated proteins were associated with microtubule dynamics (microtubule-associated proteins, Tppp, collapsin response mediator proteins) and the actin–spectrin network (e.g., spectrins, adducins, band 4.1-like protein 1). Taken together, a six-month morphine withdrawal was manifested by significant alterations in the phosphorylation of synaptic proteins. The altered phosphorylation patterns modulating the function of synaptic proteins may contribute to long-term neuroadaptations induced by drug use and withdrawal. |
| first_indexed | 2024-03-10T09:34:00Z |
| format | Article |
| id | doaj.art-0c6d555f80094c21b0e5cae5f7c1bba9 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T09:34:00Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-0c6d555f80094c21b0e5cae5f7c1bba92023-11-22T04:13:07ZengMDPI AGLife2075-17292021-07-0111768310.3390/life11070683Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from MorphineZdenka Drastichova0Lucie Hejnova1Radka Moravcova2Jiri Novotny3Department of Physiology, Faculty of Science, Charles University, 12800 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 12800 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 12800 Prague, Czech RepublicDepartment of Physiology, Faculty of Science, Charles University, 12800 Prague, Czech RepublicDrug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have not yet been fully identified. In the present study, changes in proteomic and phosphoproteomic profiles of selected brain regions (cortex, hippocampus, striatum, and cerebellum) from rats abstaining for six months after cessation of chronic treatment with morphine were determined by label-free quantitative (LFQ) proteomic analysis. Interestingly, prolonged morphine withdrawal was found to be associated especially with alterations in protein phosphorylation and to a lesser extent in protein expression. Gene ontology (GO) term analysis revealed enrichment in biological processes related to synaptic plasticity, cytoskeleton organization, and GTPase activity. More specifically, significant changes were observed in proteins localized in synaptic vesicles (e.g., synapsin-1, SV2a, Rab3a), in the active zone of the presynaptic nerve terminal (e.g., Bassoon, Piccolo, Rims1), and in the postsynaptic density (e.g., cadherin 13, catenins, Arhgap35, Shank3, Arhgef7). Other differentially phosphorylated proteins were associated with microtubule dynamics (microtubule-associated proteins, Tppp, collapsin response mediator proteins) and the actin–spectrin network (e.g., spectrins, adducins, band 4.1-like protein 1). Taken together, a six-month morphine withdrawal was manifested by significant alterations in the phosphorylation of synaptic proteins. The altered phosphorylation patterns modulating the function of synaptic proteins may contribute to long-term neuroadaptations induced by drug use and withdrawal.https://www.mdpi.com/2075-1729/11/7/683morphinewithdrawalbrainproteomicssynaptic plasticity |
| spellingShingle | Zdenka Drastichova Lucie Hejnova Radka Moravcova Jiri Novotny Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine Life morphine withdrawal brain proteomics synaptic plasticity |
| title | Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine |
| title_full | Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine |
| title_fullStr | Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine |
| title_full_unstemmed | Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine |
| title_short | Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine |
| title_sort | proteomic analysis unveils expressional changes in cytoskeleton and synaptic plasticity associated proteins in rat brain six months after withdrawal from morphine |
| topic | morphine withdrawal brain proteomics synaptic plasticity |
| url | https://www.mdpi.com/2075-1729/11/7/683 |
| work_keys_str_mv | AT zdenkadrastichova proteomicanalysisunveilsexpressionalchangesincytoskeletonandsynapticplasticityassociatedproteinsinratbrainsixmonthsafterwithdrawalfrommorphine AT luciehejnova proteomicanalysisunveilsexpressionalchangesincytoskeletonandsynapticplasticityassociatedproteinsinratbrainsixmonthsafterwithdrawalfrommorphine AT radkamoravcova proteomicanalysisunveilsexpressionalchangesincytoskeletonandsynapticplasticityassociatedproteinsinratbrainsixmonthsafterwithdrawalfrommorphine AT jirinovotny proteomicanalysisunveilsexpressionalchangesincytoskeletonandsynapticplasticityassociatedproteinsinratbrainsixmonthsafterwithdrawalfrommorphine |