Antidepressants act on glial cells: SSRIs and serotonin elicit astrocyte calcium signaling in the mouse prefrontal cortex

Item Type:	Article
Title:	Antidepressants act on glial cells: SSRIs and serotonin elicit astrocyte calcium signaling in the mouse prefrontal cortex
Creators Name:	Schipke, C.G. and Heuser, I. and Peters, O.
Abstract:	One important target in the treatment of major depressive disorder (MDD) is the serotonin (5-hydroxytryptamine, 5-HT) system. Selective serotonin reuptake inhibitors (SSRI) are used to treat MDD. Yet, the mode of action of these drugs is not completely understood. There is evolving evidence for a role of glutamate in mood disorder and its signaling. Astrocytes are involved in glutamate metabolism and play an active role in memory processing but their role in mood disorders is still largely unknown. A modulation of astrocytic signaling by SSRIs or 5-HT has not been investigated up to now. We investigated astrocytic calcium signaling with the calcium indicator dye Fluo-4. Using a confocal microscope, we imaged astrocytes in the medial prefrontal cortex of acute mouse brain slices after the application of the SSRIs citalopram and fluoxetine. In the same way, we studied the effects of serotonin and the modulation of this signaling by glutamate in astrocytes. We found that astrocyte calcium signaling can be elicited by 5-HT. Also, the SSRIs citalopram and fluoxetine induce calcium signals in about 1/3 of all astrocytes, even when neuronal signal propagation is inhibited. Astrocytic responses to 5-HT have a unique pattern and they could mostly not be evoked twice. We determined that glutamate is a substance that can interfere with 5-HT-induced calcium signals in astrocytes since after stimulation by glutamate, astrocytes did not show a response to 5-HT. Astrocytic calcium signaling is elicited by SSRIs and 5-HT. They may serve as integrators, linking the serotonergic and glutamatergic signaling pathways.
Keywords:	Astrocyte, Calcium Imaging, Cortex, Major Depressive Disorder, Serotonin, Selective Serotonin Reuptake Inhibitor, Animals, Mice
Source:	Journal of Psychiatric Research
ISSN:	0022-3956
Publisher:	Elsevier
Volume:	45
Number:	2
Page Range:	242-248
Date:	February 2011
Official Publication:	https://doi.org/10.1016/j.jpsychires.2010.06.005
PubMed:	View item in PubMed

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