PMID- 19196496
OWN - NLM
STAT- MEDLINE
DCOM- 20090605
LR  - 20161125
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 19
IP  - 5
DP  - 2009 May
TI  - Differential effects of aripiprazole and haloperidol on BDNF-mediated signal 
      changes in SH-SY5Y cells.
PG  - 356-62
LID - 10.1016/j.euroneuro.2008.12.012 [doi]
AB  - Recent studies have suggested that first and second generation antipsychotics 
      (FGAs and SGAs) have different neuroprotective effects. However, the molecular 
      mechanisms of SGAs are not fully understood, and investigations into changes in 
      intracellular signaling related to their neuroprotective effects remain scarce. 
      In the present study, we compared the SGA aripiprazole with the FGA haloperidol 
      in SH-SY5Y human neuroblastoma cells via brain-derived neurotrophic factor 
      (BDNF)-mediated signaling, notably BDNF, glycogen synthase kinase-3beta 
      (GSK-3beta), and B cell lymphoma protein-2 (Bcl-2). We examined the effects of 
      aripiprazole (five and 10 microM) and haloperidol (one and 10 microM) on BDNF 
      gene promoter activity in SH-SY5Y cells transfected with a rat BDNF promoter 
      fragment (-108 to +340) linked to the luciferase reporter gene. The changes in 
      BDNF, p-GSK-3beta, and Bcl-2 levels were measured by Western blot analysis. The 
      haloperidol was not associated with a significant difference in BDNF promoter 
      activity. In contrast, aripiprazole was associated with increased BDNF promoter 
      activity only with a dose of 10 microM (93%, p<0.01). Treatment with aripiprazole 
      at 10 microM increased the levels of BDNF by 85%, compared with control levels 
      (p<0.01), whereas haloperidol had no effect. Moreover, cells treated with 
      aripirazole effectively increased the levels of GSK-3beta phosphorylation and 
      Bcl-2 at doses of five and 10 microM (30% and 58% and 31% and 80%, respectively, 
      p<0.05 or p<0.01). However, haloperidol had no effects on p-GSK-3 beta and Bcl-2 
      expression. This study showed that aripiprazole, but not haloperidol, appeared to 
      offer neuroprotective effects on human neuronal cells. The actions of signaling 
      systems associated with BDNF may represent key targets for both aripiprazole and 
      haloperidol, but the latter may be associated with distinct effects. These 
      differences might be related to the different therapeutic effects of FGAs and 
      SGAs in patients with schizophrenia.
FAU - Park, Sung Woo
AU  - Park SW
AD  - Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
FAU - Lee, Jung Goo
AU  - Lee JG
FAU - Ha, Eun Kyung
AU  - Ha EK
FAU - Choi, Sang Mi
AU  - Choi SM
FAU - Cho, Hye Yeon
AU  - Cho HY
FAU - Seo, Mi Kyoung
AU  - Seo MK
FAU - Kim, Young Hoon
AU  - Kim YH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090203
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Piperazines)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Quinolones)
RN  - 82VFR53I78 (Aripiprazole)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - J6292F8L3D (Haloperidol)
SB  - IM
MH  - Analysis of Variance
MH  - Antipsychotic Agents/*pharmacology
MH  - Aripiprazole
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Haloperidol/*pharmacology
MH  - Humans
MH  - Luciferases/metabolism
MH  - Neuroblastoma
MH  - Piperazines/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Quinolones/*pharmacology
MH  - Signal Transduction/*drug effects
MH  - Transfection/methods
EDAT- 2009/02/07 09:00
MHDA- 2009/06/06 09:00
CRDT- 2009/02/07 09:00
PHST- 2008/11/05 00:00 [received]
PHST- 2008/12/19 00:00 [revised]
PHST- 2008/12/23 00:00 [accepted]
PHST- 2009/02/07 09:00 [entrez]
PHST- 2009/02/07 09:00 [pubmed]
PHST- 2009/06/06 09:00 [medline]
AID - S0924-977X(09)00005-4 [pii]
AID - 10.1016/j.euroneuro.2008.12.012 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2009 May;19(5):356-62. doi: 
      10.1016/j.euroneuro.2008.12.012. Epub 2009 Feb 3.