Stathmin reduction and cytoskeleton rearrangement in rat nucleus accumbens in response to clozapine and risperidone treatment – Comparative proteomic study. (1st March 2016)

• Record Type: Journal Article
• Authors: Kedracka-Krok, S.; Swiderska, B.; Jankowska, U.; Skupien-Rabian, B.; Solich, J.; Dziedzicka-Wasylewska, M.
• Is Part Of: Neuroscience. Volume 316(2016)
• Page Start: 63
• Page End: 81
• Publication Date: 2016-03-01
• Subjects: 2DE two-dimensional gel electrophoresis -- ACN acetonitrile -- AP-2 adaptor-related protein-2 -- AP2b1 AP-2 complex subunit beta -- Cdk5 cyclin-dependent kinase 5 -- CLO clozapine -- CRMPs collapsin response mediator protein family, dihydropyrimidinase-related proteins -- DA dopamine -- DARPP-32 dopamine and cyclic AMP-regulated phosphoprotein, protein phosphatase 1 regulatory subunit 1B -- DIA differential in-gel analysis -- DIGE differential in-gel electrophoresis -- DTT dithiothreitol -- EDTA ethylenediaminetetraacetic acid -- emPAI exponentially modified protein abundance index -- EPS extrapyramidal symptoms -- FGAs first-generation antipsychotics -- GSH glutathione -- GSS glutathione synthetase -- Hsp75 Heat-shock protein 75 kDa, mitochondrial -- HSPA8 heat-shock 70-kDa protein 8, heat-shock cognate 71-kDa protein -- IPA Ingenuity Pathway Analysis -- LASP-1 Lim and SH3 domain protein -- LTP long-term potentiation -- MS mass spectrometry -- MSNs medium spiny neurons -- MT microtubule -- NAc nucleus accumbens -- NF-L intermediate filament protein L, neurofilament light polypeptide -- NUBP2 cytosolic Fe–S cluster assembly factor -- PFC prefrontal cortex -- PKA protein kinase A -- Rheb Ras homolog enriched in brain, GTP-binding protein Rheb -- RIS risperidone -- SEPT6 septin 6 -- SGAs second-generation antipsychotics -- SIRT2 NAD-dependent protein deacetylase sirtuin-2 -- Stmn1 stathmin -- STRAP serine-threonine kinase receptor-associated protein -- SynII synapsin-2 -- Syt1 synaptotagmin-1 -- VS ventral striatum; nucleus accumbens -- clozapine -- risperidone -- 2D-DIGE -- stathmin -- glutathione synthetase; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.12.028
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: Risperidone and clozapine reduced stathmin levels in rat nucleus accumbens. Clozapine and risperidone affected microtubules stability in rat nucleus accumbens. Clozapine exerted neuroprotective role in rat nucleus accumbens. Risperidone changed the level of synaptic proteins in rat nucleus accumbens. 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.