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Article: Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells

TitleDifferential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells
Authors
KeywordsBDNF
c-fos
Classical and atypical antipsychotics
Intracellular calcium
PC12 cells
STAT-3
Issue Date2007
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/euroneuro
Citation
European Neuropsychopharmacology, 2007, v. 17 n. 12, p. 768-773 How to Cite?
AbstractAlthough 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 μM 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. © 2007 Elsevier B.V. and ECNP.
Persistent Identifierhttp://hdl.handle.net/10722/89629
ISSN
2015 Impact Factor: 4.409
2015 SCImago Journal Rankings: 1.851
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTan, QRen_HK
dc.contributor.authorWang, XZen_HK
dc.contributor.authorWang, CYen_HK
dc.contributor.authorLiu, XJen_HK
dc.contributor.authorChen, YCen_HK
dc.contributor.authorWang, HHen_HK
dc.contributor.authorZhang, RGen_HK
dc.contributor.authorZhen, XCen_HK
dc.contributor.authorTong, Yen_HK
dc.contributor.authorZhang, ZJen_HK
dc.date.accessioned2010-09-06T09:59:37Z-
dc.date.available2010-09-06T09:59:37Z-
dc.date.issued2007en_HK
dc.identifier.citationEuropean Neuropsychopharmacology, 2007, v. 17 n. 12, p. 768-773en_HK
dc.identifier.issn0924-977Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/89629-
dc.description.abstractAlthough 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 μM 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. © 2007 Elsevier B.V. and ECNP.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/euroneuroen_HK
dc.relation.ispartofEuropean Neuropsychopharmacologyen_HK
dc.rightsEuropean Neuropsychopharmacology. Copyright © Elsevier BV.en_HK
dc.subjectBDNFen_HK
dc.subjectc-fosen_HK
dc.subjectClassical and atypical antipsychoticsen_HK
dc.subjectIntracellular calciumen_HK
dc.subjectPC12 cellsen_HK
dc.subjectSTAT-3en_HK
dc.titleDifferential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0924-977X&volume=17&issue=12&spage=768&epage=773&date=2007&atitle=Differential+effects+of+classical+and+atypical+antipsychotic+drugs+on+rotenone-induced+neurotoxicity+in+PC12+cellsen_HK
dc.identifier.emailTong, Y: tongyao@hku.hken_HK
dc.identifier.emailZhang, ZJ: zhangzj@hkucc.hku.hken_HK
dc.identifier.authorityTong, Y=rp00509en_HK
dc.identifier.authorityZhang, ZJ=rp01297en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.euroneuro.2007.03.003en_HK
dc.identifier.pmid17442543-
dc.identifier.scopuseid_2-s2.0-35348890731en_HK
dc.identifier.hkuros135457en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35348890731&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume17en_HK
dc.identifier.issue12en_HK
dc.identifier.spage768en_HK
dc.identifier.epage773en_HK
dc.identifier.isiWOS:000251231700004-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridTan, QR=7102120177en_HK
dc.identifier.scopusauthoridWang, XZ=22836989800en_HK
dc.identifier.scopusauthoridWang, CY=35345843000en_HK
dc.identifier.scopusauthoridLiu, XJ=26428187400en_HK
dc.identifier.scopusauthoridChen, YC=22833345400en_HK
dc.identifier.scopusauthoridWang, HH=10144885500en_HK
dc.identifier.scopusauthoridZhang, RG=7404865068en_HK
dc.identifier.scopusauthoridZhen, XC=16246797700en_HK
dc.identifier.scopusauthoridTong, Y=9045384000en_HK
dc.identifier.scopusauthoridZhang, ZJ=8061473900en_HK

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