Related Experiment Videos
Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice
L K Heisler1, H M Chu, L H Tecott
1Department of Psychiatry, University of California at San Francisco 94143, USA.
Abstract:
Serotonin 5-HT2C receptor null mutant mice were generated to assess the contribution of this receptor to the actions of serotonin. Mutant mice displayed both an epilepsy and obesity phenotype. The epilepsy syndrome was characterized by spontaneous seizures, lowered seizure threshold, enhanced seizure propagation and sound-induced seizure susceptibility. These findings implicate 5-HT2C receptors in the regulation of neuronal network excitability. It was also observed that body weight and adipose tissue deposition were elevated in adult mutant mice relative to their wild type littermates. Paired-feeding studies suggest that the obesity syndrome is a result of increased food intake. In addition, mutants displayed reduced sensitivity to the appetite suppressant actions of non-specific serotonergic agonists. These studies establish a role for 5-HT2C receptors in the serotonergic regulation of body weight and food intake.
Insights
Null mutant mice lacking serotonin 5-HT2C receptors exhibit epilepsy and obesity. These findings highlight the critical role of 5-HT2C receptors in regulating neuronal excitability and appetite control.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Serotonin (5-HT) is a neurotransmitter involved in various physiological processes.
- The 5-HT2C receptor subtype's specific role in vivo remains incompletely understood.
- Understanding receptor function is crucial for developing targeted therapeutics.
Purpose of the Study:
- To investigate the in vivo function of the serotonin 5-HT2C receptor.
- To determine the contribution of 5-HT2C receptors to neurological and metabolic regulation.
- To characterize the phenotype of mice lacking functional 5-HT2C receptors.
Main Methods:
- Generation of serotonin 5-HT2C receptor null mutant mice.
- Phenotypic analysis including seizure susceptibility testing and metabolic assessments.
- Paired-feeding studies to evaluate food intake and appetite regulation.
Main Results:
- 5-HT2C receptor null mutant mice displayed spontaneous seizures, reduced seizure threshold, and enhanced seizure propagation, indicating impaired neuronal network excitability.
- Mutant mice exhibited elevated body weight and adipose tissue deposition, characteristic of obesity.
- Increased food intake contributed to the obesity phenotype, with reduced sensitivity to appetite suppressants.
Conclusions:
- Serotonin 5-HT2C receptors are essential for regulating neuronal excitability and preventing epilepsy.
- These receptors play a significant role in controlling body weight and food intake.
- The findings establish 5-HT2C receptors as key targets for managing neurological and metabolic disorders.