Serotonin Regulation by Astrocytes

Abstract

The concentration of serotonin in synaptic spaces is regulated by serotonergic neurons through a cycle of serotonin synthesis and vesicular packaging via vesicular monoamine transporter (VMAT), release, reuptake via serotonin reuptake transporter (SERT), degradation via monoamine oxidase (MAO), and repackaging in vesicles. 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. Our question was: can astrocytes also package serotonin into vesicles and release it in response to a physiological signal?Astrocytes were dissociated from 1‐3 day old rat pups and cultured. Astrocytes were then exposed to 0.3 µM‐ 100 uM serotonin for 5 hours. Immunofluorescent experiments on serotonin loaded, GFAP positive astrocytes, show an uptake of serotonin into discrete clusters which co‐localize with the VMAT protein. This localization may be due to packaging in vesicles, which is suggested by the presence of VMAT. Western blot and RT‐PCR experiments show the presence of VMAT message and protein in astrocytes. During exocytosis assays serotonin is released from astrocytes into the surrounding media, in response to a treatment with 100 uM ATP. Serotonin uptake can be inhibited by SSRI's such as fluoxetine and citalopram. These results suggest that astrocytes may be capable of packaging serotonin after reuptake, and releasing it in response to a physiological signal.