gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Artikel

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Functional serotonin receptors on microglial cells as mediators of depression depended glial tumor growth?

Funktionale Serotoninrezeptoren auf Mikrogliazellen als Mediatoren Depressions-abhängigem Glioblastomwachstum?

Meeting Abstract

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  • corresponding author M. Synowitz - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • K. Farber - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • U. Pannasch - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • G. Kronenberg - Klinik und Poliklinik für Neurologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Deutschland
  • D. Markovic - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • N. van Rooijen - Molecular Department of Molecular Cell Biology, University of Amsterdam, Amsterdam, The Netherlands
  • B. Engels - Molekulare Zellbiologie und Gentherapie, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland *Respective authors equally contributed to this work
  • W. Uckert - Molekulare Zellbiologie und Gentherapie, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • R. Glass - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • C. Bhagat - Molekularbiologie von Hormonen, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • M. Bader - Molekularbiologie von Hormonen, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland
  • M. Endres - Klinik und Poliklinik für Neurologie, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Deutschland
  • H. Kettenmann - Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocP 075

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc330.shtml

Veröffentlicht: 11. April 2007

© 2007 Synowitz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

Objective: Depression is a common complication in patients with high grade glioma. In the present study, we have addressed the question whether modulation of serotonin receptors affect glioblastoma – host interaction.

Methods: Expression of serotonin receptors were examined by western blot analysis, immunocytochemistry, and immunofluorescent double staining in mice glial tumor cells, primary cultures of mice neuroglia and human tumor material. Organotypical brain slice culture experiments using specific agonists and antagonist, patch clamp experiments and glioma bearing mice survival studies using citalopram as SSRI were used for functional testing.

Results: Here we report that serotonin inhibits glioma growth as studied in an organotypical brain slice culture and inoculated with G261 glioma cells. When the brain slices were depleted of microglia, serotonin did no longer affect glioma growth indicating that serotonin acts on microglial cells. 5HT2A receptors were prominently expressed by tumor and microglial cells in culture and in vivo. Tumor cells triggered the upregulation of 5HT2A expression in microglia as determined by coculture experiments or analyzing tissue from an experimental rat glioma model. Using the patch-clamp technique as an assay to identify functional serotonin receptors in microglia, we recorded responses to serotonin and the specific agonists of the serotonin receptor subtypes 5HT1, 5HT2A, 5HT3 and 5HT4. Serotonin and the specific agonists reduced the constitutive inward K+ conductance and, in a subpopulation of microglia, activated an outward K+ current. Serotonin also stimulated intracellular Ca2+ increase. The anti-depressive drug citalopram, which increases the brain serotonin level, attenuated experimental glioma growth and improved survival. This effect of serotonin required the presence of microglial cells. Furthermore glioma attract microglia by release of IL-6 and serotonin receptor activation blocked this chemoattraction of microglia.

Conclusions: We conclude that microglial cells express functional serotonin receptors which are mediators to influence glioma growth. Consistently, microglial cells accumulate less around glioma in the presence of citalopram. Since the presence of microglial cells promotes tumor growth, their reduced recruitment due to the anti-depressive drug could be a new avenue for glioma therapy.

*Authors 1 and 2 equally contributed to this work