title: Stathmin reduction and cytoskeleton rearrangement in rat nucleus accumbens in response to clozapine and risperidone treatment - Comparative proteomic study.
abstract: The complex network of anatomical connections of the nucleus accumbens (NAc) makes it an interface responsible for the selection and integration of cognitive and affective information to modulate appetitive or aversively motivated behaviour. There is evidence for NAc dysfunction in schizophrenia. NAc also seems to be important for antipsychotic drug action, but the biochemical characteristics of drug-induced alterations within NAc remain incompletely characterized. In this study, a comprehensive proteomic analysis was performed to describe the differences in the mechanisms of action of clozapine (CLO) and risperidone (RIS) in the rat NAc. Both antipsychotics influenced the level of microtubule-regulating proteins, i.e., stathmin, and proteins of the collapsin response mediator protein family (CRMPs), and only CLO affected NAD-dependent protein deacetylase sirtuin-2 and septin 6. Both antipsychotics induced changes in levels of other cytoskeleton-related proteins. CLO exclusively up-regulated proteins involved in neuroprotection, such as glutathione synthetase, heat-shock 70-kDa protein 8 and mitochondrial heat-shock protein 75. RIS tuned cell function by changing the pattern of post-translational modifications of some proteins: it down-regulated the phosphorylated forms of stathmin and dopamine and the cyclic AMP-regulated phosphoprotein (DARPP-32) isoform but up-regulated cyclin-dependent kinase 5 (Cdk5). RIS modulated the level and phosphorylation state of synaptic proteins: synapsin-2, synaptotagmin-1 and adaptor-related protein-2 (AP-2) complex.
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Department of Structural Biology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: sylwia.kedracka-krok@uj.edu.pl.
authors.forename: S
authors.initials: S
authors.lastname: Kedracka-Krok
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Swiderska
authors.affiliation: Department of Structural Biology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: U
authors.initials: U
authors.lastname: Jankowska
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Skupien-Rabian
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Solich
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland; Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology*; D050777:Stathmin / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D050777:Stathmin; D051360:Cyclin-Dependent Kinase 5; D003024:Clozapine; D018967:Risperidone; D004298:Dopamine
keywords: 2D-DIGE; clozapine; glutathione synthetase; nucleus accumbens; risperidone; stathmin