Microarray analysis reveals distinct gene expression patterns in the mouse cortex following chronic neuroleptic and
C Mehler-Wex1, E Grünblatt, S Zeiske
1Department of Child and Adolescent Psychiatry, University of Würzburg, Germany. mehler@kjp.uni-wuerzburg.de
Abstract:
Atypical neuroleptics are associated with clinical significant weight gain, whereas stimulants are used as anorexiant drugs. The aim of this study was to examine gene expression changes in the mouse frontal cortex following chronic oral treatment with antipsychotics and a stimulant by microarray assessments. Twenty 10-12-week-old male C57BL6 mice received daily for 31 days either the typical neuroleptic haloperidol (1 mg/kg), the atypical neuroleptic clozapine (10 mg/kg) or the stimulant phenylpropanolamine (3 mg/kg). We identified a set of genes that was differently expressed between the neuroleptic-treated groups and the stimulant-treated group. Importantly, we found in the majority of gene alterations down-regulation in genes involved in ATP biosynthesis and lipid metabolism following the stimulant treatment, suggesting these genes as candidates that may regulate body weight. We also identified remarkable expression patterns of genes that encode signalling molecules (e.g. insulin, mitochondrial uncoupling protein 1) that are implicated in the control of food intake and are differently expressed in the neuroleptic groups.
Insights
Stimulant drugs may regulate body weight by down-regulating genes involved in ATP biosynthesis and lipid metabolism. Neuroleptics showed different gene expression patterns, impacting food intake signaling molecules.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Atypical neuroleptics are linked to significant weight gain.
- Stimulants are recognized for their anorexiant properties.
- Understanding drug-induced gene expression changes is crucial for metabolic research.
Purpose of the Study:
- To investigate gene expression alterations in the mouse frontal cortex after chronic antipsychotic and stimulant administration.
- To identify candidate genes involved in body weight regulation influenced by these drug classes.
Main Methods:
- Microarray analysis of gene expression in the frontal cortex of C57BL6 mice.
- Chronic oral administration of haloperidol (typical neuroleptic), clozapine (atypical neuroleptic), and phenylpropanolamine (stimulant) for 31 days.
Main Results:
- Distinct gene expression profiles were observed between neuroleptic-treated and stimulant-treated groups.
- Phenylpropanolamine treatment led to down-regulation of genes in ATP biosynthesis and lipid metabolism.
- Neuroleptic treatment altered the expression of genes encoding signaling molecules like insulin and mitochondrial uncoupling protein 1, implicated in food intake control.
Conclusions:
- Genes involved in ATP biosynthesis and lipid metabolism are potential regulators of body weight following stimulant treatment.
- Differential expression of signaling molecules by neuroleptics suggests a role in modulating food intake.
- This study provides insights into the molecular mechanisms underlying drug-induced weight changes.
