Antipsychotic drugs induce cell cytoskeleton reorganization in glial and neuronal cells via Rho/Cdc42 signal pathway.
Long-term administration of antipsychotic drugs (APDs) has been theorized to effect drug-induced changes in protein expression in the brain. Our previous findings revealed that ADPs can regulate Rho GDP-dissociation inhibitor 1 (RhoGDI1) expression in glial cells. To reveal whether APDs (haloperidol, risperidone, and clozapine) might regulate cell functions in rat brain by affecting RhoGDI1, RhoGDI1 regulation, RhoGDI1-related Rho family protein, and also MLC2 in brain of 7-day APD treatment rat were examined. Increased expression of RhoGDI1 and RhoA and decreased expression of MLC2, p-MLC2 and ARP2/3 were found in the cortex of APD-treated rats. The activation of RhoA in APD-treated rat cortex was also found. The regulation of RhoGDI1-induced protein expression and its relation to intracellular stress filament production and cell migration were further examined in APD-treated C6 and B35 cells. APD-induced RhoA expression and activation in C6 cells and Cdc42 expression and activation in B35 cells were investigated. In C6 cells, ARP2/3, ROCK1, pMLC2, and PFN1 expressions were decreased, and N-WASP expression was increased by any of the three APDs. In B35 cells, haloperidol decreased ROCK1 expression, but risperidone increased ROCK1 expression. MLC2, p-MLC2, and PFN1 expressions were decreased in B35 cells treated with either risperidone or clozapine. N-WASP expression was decreased by haloperidol and clozapine. We also found all three APDs enhance C6 and B35 F-actin condensation and migration ability.
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan, ROC. Electronic address: cater0656@hotmail.com.
Mao-Liang
ML
Chen
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan, ROC; Department of Microbiology, Soochow University, Shih Lin, Taipei, Taiwan, ROC.
Fu-Ming
FM
Tsai
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan, ROC.
Ming-Cheng
MC
Lee
Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan, ROC.
Yi-Yin
YY
Lin
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000235:genetics / Q000378:metabolism*
D014150:Antipsychotic Agents; D012333:RNA, Messenger; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D012694:Serine
Antipsychotics; Cdc42; Cytoskeleton; MLC2; RhoA; RhoGDI1