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1. Serotonin
2. Mouse Model
3. Applications & Clinical Implications
4. Clinical research
The serotonin system
The broad goal of our studies is a better understanding of the entire serotonin (5-HT) neurotransmitter system and its contributions to physiology, behavior and human disorders, especially neuropsychiatric disorders. Serotonin has been implicated in almost every physiological function known.The serotonin transporter (SERT) recycles serotonin by returning serotonin to presynaptic vesicles after its release, thereby terminating the action of serotonin at its receptors. Serotonin's 14-plus receptors are target molecules for the largest numbers of neuropsychiatric drugs used in the world.
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Mouse model
In our attempt to better understand serotonin's function, we have generated a mouse model which either lacks the serotonin transporter completely or has a 50% reduction in serotonin transporter expression. These SERT -/- and +/- mice have gene-proportionate increases in the extracellular fluid serotonin (5-HT) concentrations, i.e., 9- and 5-fold excesses respectively over +/+ mice, with the SERT deficiency present since conception. We have also studied mouse neural stem cells as potential steps toward serotonin system gene therapy.
Research application
To explore just what serotonin does in normal physiology and in disease - this mouse model is providing an experimental window not previously
available to test hypotheses about serotonin's contributions to multiple
biological processes and human disorders.
Applications and clinical implications
Our mouse model also provides an opportunity to further elucidate physiological control mechanisms, neuroanatomical development, emotional states, and drug effects.
Clinical research
Serotonin function is thought to be involved in many normal human physiological functions and behaviors and many neuropsychiatric and other medical disorders. Therefore, we are conducting genetic and phenomenological studies of obsessive-compulsive disorder and related disorders such as Tourette's Syndrome, compulsive hoarding, depression, and other related problems thought to involve serotonin. These studies are being accomplished both at our NIMH, Bethesda laboratory and in conjunction with other genetic groups (such as the , OCD Collaborative Genetics Study and the Obsessive-Compulsive Disorder Foundation Genetics Consortium) plus other individual geneticists at NIH and worldwide. These studies have also been extended into other genes which are beginning to be implicated in these disorders. such as BDNF and the neuronal glutamate transporter gene, SLC6A4.
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