Serotonin regulation by primary culture neonatal rat astrocytes

Alexander Ferrazzoli and Cheryl Watson, Department of Biomolecular Sciences, Central Connecticut State University

Many psychiatric disorders are linked to abnormal synaptic serotonin concentration levels. The concentration of serotonin in synaptic spaces is regulated by serotonergic neurons through a cycle of serotonin synthesis and vesicular packaging via VMAT, calcium-mediated release, reuptake via SERT, degradation via MAO, and repackaging in vesicles via VMAT. Astrocytes are also known to contribute to the regulation of synaptic serotonin concentration through uptake of serotonin via SERT, and the subsequent degradation by MAO. This uptake via SERT is inhibited by SSRIs. This project began by investigating the effect of SSRIs on SERT expression in astrocytes through immunofluorescent microscopy. Astrocytes are dissociated from 13 day old rat pups, cultured for approximately 10 days, and then exposed to 0.3 M serotonin for 2 hours. Preliminary results have uncovered localization of serotonin in astrocytes after uptake. This localization may be due to packaging in vesicles via VMAT, as seen in serotonergic neurons. We have probed GFAP-positive astrocytes with antibodies for serotonin and VMAT, and found co-localization of both. These results suggest that astrocytes may be capable of packaging serotonin after reuptake. We are currently verifying the presence of VMAT expression in astrocytes through RT-PCR. These studies may help identify new targets for the development of psychiatric treatments.

Presented April 30, 2007 at the Experimental Biology (FASEB) Annual Meeting, Washington DC