title: 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.affiliation: †Pharmacology Laboratory, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vicente-Rodríguez
authors.affiliation: †Pharmacology Laboratory, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Herradón
authors.affiliation: ‡BRAINco Biopharma, S.L., Bizkaia Technology Park, Vizcaya, Spain.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ferrer-Alcón
authors.affiliation: ‡BRAINco Biopharma, S.L., Bizkaia Technology Park, Vizcaya, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Uribarri
authors.affiliation: †Pharmacology Laboratory, Department of Pharmaceutical and Health Sciences, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pérez-García
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003042:Cocaine / Q000633:toxicity*; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D020543:Proteome / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D020543:Proteome; C066845:pleiotrophin; D003042:Cocaine