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Twelve weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA).

ABSTRACT: Atypical antipsychotic Clozapine has a superior antipsychotic and antimanic effects compared to other antisphicotics. Its widespread use was limited by the side effects of agranulocytosis, cardiomyopathy and metabolic anomalies such as weight gain, and diabetes. Very little is known about mechanisms by which Clozapine works. The aim of this experiment is to compare the chronic gene expression profile of the atypical antipsychotic Clozapine to the typical antipsychotic drug Haloperidol using gene expression Microarray in order to understand the intercellular mechanism behind the therapeutic and the toxic effects of Clozapine. Keywords: drug response

ORGANISM(S): Mus musculus

PROVIDER: GSE6467 | GEO | 2006/12/13

SECONDARY ACCESSION(S): PRJNA104237

REPOSITORIES: GEO

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Transcription profiling of mouse brain after twelve week treatment with the antipsychotics Clozapine and Haloperidol

Project description:Atypical antipsychotic Clozapine has a superior antipsychotic and antimanic effects compared to other antisphicotics. Its widespread use was limited by the side effects of agranulocytosis, cardiomyopathy and metabolic anomalies such as weight gain, and diabetes. Very little is known about mechanisms by which Clozapine works. The aim of this experiment is to compare the chronic gene expression profile of the atypical antipsychotic Clozapine to the typical antipsychotic drug Haloperidol using gene expression Microarray in order to understand the intercellular mechanism behind the therapeutic and the toxic effects of Clozapine. Experiment Overall Design: The study was designed to compare the chronic therapeutic and toxic expression profile of Clozapine to Haloperidol in the mouse brain. All experiments were performed in male C57BL mice at four weeks of age (Biological services, University Collage London). Several theoretical and practical considerations influenced the final experimental design. To avoid the effect of injections on genes expression and to simulate the clinical scenario in human, both drugs were applied to the animals drinking water using the maximum human therapeutic dose (i.e. 1.6mg/kg/day for Haloperidol and 12mg/kg/day for Clozapine). Thirty animals were divided equally between three treatment groups and received either Haloperidol (10 animals), Clozapine (10 animals) or no treatment (10 animals) for 12 weeks. After twelve weeks, the total RNA from the right forebrains were extracted and hybridized to the Affymetrix MOE430A array. In all the Microarray experiments we have avoided pooling and each RNA sample was an independent biological replicate. The total numbers of used arrays were 30 Affymetrix MOE430A arrays.

2009-02-07 | E-GEOD-6467 | biostudies-arrayexpress

Four weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA).

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Transcription profiling of mouse brain from animals treated for 4 weeks with the antipsychotics Clozapine and Haloperidol

Project description:Atypical antipsychotic Clozapine has a superior antipsychotic and antimanic effects compared to other antisphicotics. Its widespread use was limited by the side effects of agranulocytosis, cardiomyopathy and metabolic anomalies such as weight gain, and diabetes. Very little is known about mechanisms by which Clozapine works. The aim of this experiment is to compare the chronic gene expression profile (i.e four weeks) of the atypical antipsychotic Clozapine to the typical antipsychotic drug Haloperidol using gene expression Microarray in order to understand the intercellular mechanism behind the therapeutic and the toxic effects of Clozapine. Experiment Overall Design: The study was designed to compare the chronic therapeutic and toxic expression profile of Clozapine to Haloperidol in the mouse brain. All experiments were performed in male C57BL mice at four weeks of age (Biological services, University Collage London). Several theoretical and practical considerations influenced the final experimental design. To avoid the effect of injections on genesâ expression and to simulate the clinical scenario in human, both drugs were applied to the animalsâ drinking water using the maximum human therapeutic dose (i.e.1.6mg/kg/day for Haloperidol and 12mg/kg/day for Clozapine).Thirty animals were divided equally between three treatment groups and received either Haloperidol (10 animals), Clozapine (10 animals) or no treatment (10 animals) for 4 weeks. After four weeks,the plasma drug level for both drugs was assesed by Tandem mass Spectrometry LC- MS/MS. The total RNA from the right forebrains of nine selected animals (three from each treatment group) were extracted and hybridized to the Affymetrix U74Av2. In all the Microarray experiments we have avoided pooling and each RNA sample was an independent biological replicate. The total numbers of used arrays were 9 Affymetrix U74Av2.

2009-04-30 | E-GEOD-6511 | biostudies-arrayexpress

Transcription profiling of mouse brain treated with clozapine and haloperidol

Project description:This SuperSeries is composed of the following subset Series:; GSE6467: Twelve weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA). GSE6511: Four weeks expression data of the antipsychotics Clozapine and Haloperidol in the mouse brain (Affymetrix, GCRMA). Experiment Overall Design: Refer to individual Series

2008-06-14 | E-GEOD-6512 | biostudies-arrayexpress

Evaluation and mechanism study of cardiotoxicity caused by antipsychotics using human-induced pluripotent stem cell-derived cardiomyocytes

Project description:In this study, a comprehensive evaluation model for studying the cardiac toxicity of antipsychotic drugs was established by using iPSC-CMs. Six antipsychotic drugs, including aripiprazole, risperidone, quetiapine, haloperidol, clozapine, and olanzapine, all induced concentration-dependent QT prolongation in iPSC-CMs upon acute administration, and high concentrations of these drugs caused disorganized sarcomere arrangement in iPSC-CMs.

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Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids

Project description:Clozapine is an atypical antipsychotic drug for treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude a more common use as a first-line therapy of schizophrenia. Toxicoproteomics approaches have been demonstrated to effectively guide the identification of toxicological mechanisms. Here, to further our understanding of Clozapine's molecular effects we performed a Data-independent Acquisition (DIA)-based quantitative proteomics investigation of Clozapine-treated human liver spheroid cultures. In total, we quantified 4,479 proteins across five treatment groups (vehicle, 15 µM, 30 µM, 60 µM Clozapine, and 10 ng/mL TNFa + IL-1a). 60 µM Clozapine treatment yielded 36 differentially expressed proteins (fdr < 0.05). Gene-set enrichment analysis indicated perturbation of several gene-sets, which included interferon gamma signaling (e.g., IFNGR1) and prominently autophagy related processes (e.g., upregulation of SQSTM1, MAP1LC3B/LC3B2, GABARAPL2, and NCOA4). Clozapine's effects on autophagy were confirmed using conventional SQSTM1 and LC3B markers by targeted mass-spectrometry and Western Blot.

2022-12-09 | PXD034257 | Pride

Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids

Project description:Clozapine is an atypical antipsychotic drug used to treat treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude its more common use as a first-line therapy for schizophrenia. Toxicoproteomic approaches have been demonstrated to effectively guide the identification of toxicological mechanisms. Here, to further our understanding of the molecular effects of clozapine, we performed a data-independent acquisition (DIA)-based quantitative proteomics investigation of clozapine-treated human liver spheroid cultures. In total, we quantified 4,479 proteins across the five treatment groups (vehicle; 15 µM, 30 µM, and 60 µM clozapine; and 10 ng/mL TNFα + IL-1β). Clozapine (60 µM) treatment yielded 36 differentially expressed proteins (FDR < 0.05). Gene-set enrichment analysis indicated perturbation of several gene sets, including interferon gamma signaling (e.g., interferon gamma receptor 1) and prominent autophagy-related processes (e.g., upregulation of sequestosome-1 (SQSTM1), MAP1LC3B/LC3B2, GABARAPL2, and nuclear receptor coactivator 4). The effects of clozapine on autophagy were confirmed by targeted mass spectrometry and western blotting using conventional SQSTM1 and LC3B markers. Combined with prior literature, our work suggests a broad contribution of autophagy to both the therapeutic and side effects of clozapine. Overall, this study demonstrates how proteomics can contribute to the elucidation of physiological and toxicological mechanisms of drugs.

2022-12-13 | PXD038007 | Pride

Chronic haloperidol effects on gene expression in mouse [array]

Project description:We evaluate the effects of chronic administration of antipsychotic haloperidol versus placebo in male, 8-week old, C57BL/6J mice. We used microarray to study gene expression changes after haloperidol treatment in mouse brain and liver

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Clozapine and Haloperidol effect on the mouse brain

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