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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Cytoskeletal genes regulation by chronic morphine treatment in rat striatum
Cynthia Marie-Claire1, Cindie Courtin, Bernard P Roques
1Departement de Pharmacochimie Moleculaire et Structurale, Universite Rene Descartes-Paris V, Paris, France. marie@pharmacie.univ-paris5.fr
Abstract:
It has been previously suggested that morphine can regulate the expression and function of some proteins of the cytoskeleton. In the present study, we used real-time quantitative polymerase chain reaction to examine the effects of chronic morphine administration, in rat striatum, on 14 proteins involved in microtubule polymerization and stabilization, intracellular trafficking, and serving as markers of neuronal growth and degeneration. Chronic morphine treatment led to modulation of the mRNA level of seven of the 14 genes tested. Glial fibrillary acidic protein (Gfap) and activity-regulated cytoskeleton-associated protein (Arc) mRNA were upregulated, while growth associated protein (Gap43), clathrin heavy chain (Cltc), alpha-tubulin, Tau, and stathmin were downregulated. In order to determine if the regulation of an mRNA correlates with a modulation of the expression of the corresponding protein, immunoblot analyses were performed. With the exception of Gap43, the levels of Cltc, Gfap, Tau, stathmin, and alpha-tubulin proteins were found to be in good agreement with those from mRNA quantification. These results demonstrate that neuroadaptation to chronic morphine administration in rat striatum implies modifications of the expression pattern of several genes and proteins of the cytoskeleton and cytoskeleton-associated components.
Insights
Chronic morphine use alters cytoskeleton proteins in rat brains. This study found changes in mRNA and protein levels for key cytoskeletal components, indicating neuroadaptation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Morphine is known to affect cellular processes.
- Cytoskeletal proteins play crucial roles in neuronal function, trafficking, and structural integrity.
Purpose of the Study:
- To investigate the impact of chronic morphine administration on the expression of 14 key cytoskeletal proteins in the rat striatum.
- To determine if changes in mRNA levels correlate with protein expression levels.
Main Methods:
- Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure mRNA levels.
- Immunoblot analyses were performed to assess protein expression levels.
Main Results:
- Chronic morphine treatment modulated the mRNA levels of seven out of 14 tested genes.
- Glial fibrillary acidic protein (Gfap) and activity-regulated cytoskeleton-associated protein (Arc) mRNA were upregulated.
- Growth associated protein (Gap43), clathrin heavy chain (Cltc), alpha-tubulin, Tau, and stathmin mRNA were downregulated.
- Protein levels generally correlated with mRNA changes, except for Gap43.
Conclusions:
- Neuroadaptation to chronic morphine involves significant modifications in the expression of cytoskeletal and associated proteins in the rat striatum.
- These findings highlight the molecular mechanisms underlying the brain's response to chronic opioid exposure.
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