Induction of neuronal vascular endothelial growth factor expression by cAMP in the dentate gyrus of the hippocampus is required for antidepressant-like behaviors

Jeong Sik Lee, Deok Jin Jang, Nuribalhae Lee, Hyoung Gon Ko, Hyoung Kim, Yong Seok Kim, Byungwoo Kim, Junehee Son, Hyun Kim Sung, Heekyoung Chung, Mun Yong Lee, Ryoung Kim Woon, Woong Sun, Min Zhuo, Ted Abel, Bong Kiun Kaang, Hyeon Son

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Abstract

The cAMP cascade and vascular endothelial growth factor (VEGF) are critical modulators of depression. Here we have tested whether the antidepressive effect of the cAMP cascade is mediated by VEGF in the adult hippocampus. We used a conditional genetic system in which the Aplysia octopamine receptor (Ap oa 1), a Gs-coupled receptor, is transgenically expressed in the forebrain neurons of mice. Chronic activation of the heterologous Ap oa 1 by its natural ligand evoked antidepressant-like behaviors, accompanied by enhanced phosphorylation of cAMP response element-binding protein and transcription of VEGF in hippocampal dentate gyrus (DG) neurons. Selective knockdown of VEGF in these cells during the period of cAMP elevation inhibited the antidepressant-like behaviors. These findings reveal a molecular interaction between the cAMP cascade and VEGF expression, and the pronounced behavioral consequences of this interaction shed light on the mechanism underlying neuronal VEGF functions in antidepression.

Original languageEnglish
Pages (from-to)8493-8505
Number of pages13
JournalJournal of Neuroscience
Volume29
Issue number26
DOIs
Publication statusPublished - 2009 Jul 1

ASJC Scopus subject areas

  • Neuroscience(all)

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    Lee, J. S., Jang, D. J., Lee, N., Ko, H. G., Kim, H., Kim, Y. S., Kim, B., Son, J., Sung, H. K., Chung, H., Lee, M. Y., Woon, R. K., Sun, W., Zhuo, M., Abel, T., Kaang, B. K., & Son, H. (2009). Induction of neuronal vascular endothelial growth factor expression by cAMP in the dentate gyrus of the hippocampus is required for antidepressant-like behaviors. Journal of Neuroscience, 29(26), 8493-8505. https://doi.org/10.1523/JNEUROSCI.1321-09.2009