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Clozapine influences cytoskeleton structure and calcium homeostasis in rat cerebral cortex and has a different proteomic profile than risperidone
Author(s) -
KedrackaKrok Sylwia,
Swiderska Bianka,
Jankowska Urszula,
SkupienRabian Bozena,
Solich Joanna,
Buczak Katarzyna,
DziedzickaWasylewska Marta
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13007
Subject(s) - calcium binding protein , cytoskeleton , microbiology and biotechnology , biology , clozapine , pharmacology , chemistry , biochemistry , calcium , schizophrenia (object oriented programming) , medicine , cell , psychiatry
For over the last 50 years, the molecular mechanism of anti‐psychotic drugs' action has been far from clear. While risperidone is very often used in clinical practice, the most efficient known anti‐psychotic drug is clozapine (CLO). However, the biochemical background of CLO's action still remains elusive. In this study, we performed comparative proteomic analysis of rat cerebral cortex following chronic administration of these two drugs. We observed significant changes in the expression of cytoskeletal, synaptic, and regulatory proteins caused by both antipsychotics. Among other proteins, alterations in collapsin response mediator proteins, CRMP 2 and CRMP 4, were the most spectacular consequences of treatment with both drugs. Moreover, risperidone increased the level of proteins involved in cell proliferation such as fatty acid‐binding protein‐7 and translin‐associated factor X. CLO significantly up‐regulated the expression of visinin‐like protein 1, neurocalcin δ and mitochondrial, stomatin‐like protein 2, the calcium‐binding proteins regulating calcium homeostasis, and the functioning of ion channels and receptors.Using two‐dimensional differential electrophoresis, we demonstrate that chronic treatment the healthy rats with anti‐psychotics, clozapine and risperidone, induce changes in expression of cytoskeletal, synaptic, and regulatory proteins in the cerebral cortex. While risperidone increases the level of proteins regulating cell proliferation, namely, fatty acid‐binding protein‐7 and translin‐associated factor X, the clozapine significantly up‐regulates calcium sensors, i.e., visinin‐like protein 1 and neurocalcin δ. 2D DIGE, Differential in Gel Electrophoresis; Cy2, Cy3, and Cy5 are cyanine dyes.