Transcription profiling of mouse brain treated with clozapine and haloperidol
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Mie Rizig
PROVIDER: E-GEOD-6512 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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.
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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.
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