Chronic Cocaine Use Causes Changes in the Striatal Proteome Depending on the Endogenous Expression of Pleiotrophin.

Abstract

The neurotrophic factor pleiotrophin (PTN) is upregulated in different brain areas after the administration of different drugs of abuse, including psychostimulants. PTN has been shown to prevent cocaine-induced cytotoxicity in NG108-15 and PC12 cells. We previously demonstrated that specific phosphoproteins related to neurodegeneration processes are differentially regulated in the mouse striatum by a single cocaine (15 mg/kg) administration depending on the endogenous expression of PTN. Since neurodegenerative processes are usually observed in patients exposed to toxicants for longer duration, we have now performed a striatal proteomic study using samples enriched in phosphorylated proteins from PTN knockout (PTN-/-) mice, from mice with transgenic PTN overexpression (PTN-Tg) in the brain, and from wild type (WT) mice after a chronic treatment with cocaine (15 mg/kg/day for 7 days). We have successfully identified 23 proteins significantly affected by chronic cocaine exposure, genotype, or both. Most of these proteins, including peroxiredoxin-6 (PRDX6), triosephosphate isomerase (TPI1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), and annexins A5 (ANXA5) and A7 (ANXA7), may be of significant importance because they were previously identified in proteomic studies in animals treated with psychostimulants and/or because they are related to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. The data support a protective role of PTN against chronic cocaine-induced neural alterations.

• Authors: Marta Vicente-Rodríguez, Gonzalo Herradón, Marcel Ferrer-Alcón, María Uribarri, Carmen Pérez-García
• Journal: Chemical research in toxicology (Chem Res Toxicol) Vol. 28 Issue 7 Pg. 1443-54 (Jul 20 2015) ISSN: 1520-5010 [Electronic] United States
• PMID: 26046300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Cytokines
• Proteome
• pleiotrophin
• Cocaine

Topics

• Animals
• Brain (metabolism)
• Carrier Proteins (genetics, metabolism)
• Cocaine (toxicity)
• Cytokines (deficiency, genetics, metabolism)
• Electrophoresis, Gel, Two-Dimensional
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• PC12 Cells
• Phosphorylation (drug effects)
• Proteome (drug effects, metabolism)
• Rats
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization