PMID- 17442543
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20131121
IS  - 0924-977X (Print)
IS  - 0924-977X (Linking)
VI  - 17
IP  - 12
DP  - 2007 Dec
TI  - Differential effects of classical and atypical antipsychotic drugs on 
      rotenone-induced neurotoxicity in PC12 cells.
PG  - 768-73
AB  - Although classical and atypical antipsychotics may have different effects against 
      neurotoxicity, the underlying mechanisms remain to be elucidated. In the present 
      study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and 
      quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing 
      cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12 
      cells. We also determined whether there were differential effects of RIP and HAL 
      on the expression of brain-derived neurotrophic factor (BDNF), signal transducers 
      and activators of transcription-3 (STAT-3), and the immediate early gene c-fos, 
      as well as intracellular levels of calcium. Exposure to 6 muM rotenone for 24 h 
      resulted in a significant decrease in cell viability and apoptotic alteration. 
      The rotenone-induced cytotoxicity was dose-dependently worsened by pretreatment 
      with HAL, but significantly improved by the aforementioned atypical agents at low 
      doses. Real-time PCR analysis revealed that HAL pretreatment significantly 
      increased BDNF mRNA expression but did not alter c-fos and STAT-3 expression 
      compared to rotenone-exposed cells. Unlike HAL, RIP pretreatment produced a 
      significant elevation of all the three substance mRNA expression and the 
      expression intensity was 2.6- to 4.6-fold greater than HAL. Pretreatment with 
      RIP, but not HAL, also effectively prevented an elevation of intracellular levels 
      of calcium provoked by rotenone. These results suggest that the protective 
      effects of atypical antipsychotics are associated with a greater capacity to 
      enhance pro-cell survival factors, therapeutic biomarker expression, and blockade 
      of calcium influx. This may provide an alternative for explaining therapeutic 
      advantages of atypical agents observed in clinical use.
FAU - Tan, Qing-Rong
AU  - Tan QR
AD  - Department of Psychiatry, Xijing Hospital, The Fourth Military Medical 
      University, Xi'an, Shaanxi 710032, China. tanqingr@fmmu.edu.cn
FAU - Wang, Xin-Zhao
AU  - Wang XZ
FAU - Wang, Chuan-Yue
AU  - Wang CY
FAU - Liu, Xiao-Jun
AU  - Liu XJ
FAU - Chen, Yun-Chun
AU  - Chen YC
FAU - Wang, Huai-Hai
AU  - Wang HH
FAU - Zhang, Rui-Guo
AU  - Zhang RG
FAU - Zhen, Xue-Chu
AU  - Zhen XC
FAU - Tong, Yao
AU  - Tong Y
FAU - Zhang, Zhang-Jin
AU  - Zhang ZJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070417
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neurotoxins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 03L9OT429T (Rotenone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antidepressive Agents/*classification/*pharmacology
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Calcium/metabolism
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Gene Expression Regulation/drug effects
MH  - Neurotoxins/*toxicity
MH  - PC12 Cells/*drug effects
MH  - Proto-Oncogene Proteins c-fos/genetics/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Rotenone/*toxicity
MH  - STAT3 Transcription Factor/genetics/metabolism
EDAT- 2007/04/20 09:00
MHDA- 2008/02/15 09:00
CRDT- 2007/04/20 09:00
PHST- 2006/08/24 00:00 [received]
PHST- 2007/01/15 00:00 [revised]
PHST- 2007/03/06 00:00 [accepted]
PHST- 2007/04/20 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2007/04/20 09:00 [entrez]
AID - S0924-977X(07)00062-4 [pii]
AID - 10.1016/j.euroneuro.2007.03.003 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2007 Dec;17(12):768-73. doi: 
      10.1016/j.euroneuro.2007.03.003. Epub 2007 Apr 17.