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Brain Res. 2017 Jan 15;1655:114-121. doi: 10.1016/j.brainres.2016.11.021. Epub 2016 Nov 25.

Roles of the serotonin 5-HT4 receptor in dendrite formation of the rat hippocampal neurons in vitro.

Author information

1
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
2
University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan. Electronic address: tshiga@md.tsukuba.ac.jp.

Abstract

Serotonin (5-HT) is involved in various aspects of hippocampal development, although the specific roles of 5-HT receptors are poorly understood. We investigated the roles of 5-HT receptors in the dendrite formation of hippocampal neurons. We focused on the 5-HT4 receptor, which is coupled with Gs protein, and compared the effects with those of the Gi-coupled 5-HT1A receptor. Neurons from rat hippocampi at embryonic day 18 were dissociated and treated for 4 days with the 5-HT4 receptor agonist BIMU8 or the 5-HT1A receptor agonist 8-OH DPAT. The formation of primary dendrites and dendrite branching were promoted by BIMU8, whereas the dendrite branching was inhibited by 8-OH DPAT. BIMU8-induced promotion of dendrite formation was neutralized by concomitant treatment with the 5-HT4 receptor antagonist, confirming the specific actions of the 5-HT4 receptor. We then examined the signaling mechanisms underlying the actions of the 5-HT4 receptor by using a protein kinase A (PKA) inhibitor. The BIMU8-induced promotion of dendrite formation was reversed partially by the PKA inhibitor, suggesting involvement of PKA signaling downstream of the 5-HT4 receptor. Finally, we examined the contribution of brain-derived neurotrophic factor (BDNF) to the promotion of dendrite formation by BIMU8. Quantitative RT-PCR analysis showed that BIMU8 increased the BDNF mRNA expression and that treatment of cultured neurons with the TrkB antagonist reversed the BIMU8-induced increase in dendrite formation. In summary, the present study suggests a novel role for the 5-HT4 receptor in facilitation of dendrite formation in which intracellular signaling of PKA and the BDNF-TrkB system may be involved.

KEYWORDS:

Dendrite formation; Dissociated cell culture; Hippocampus; Serotonin; Serotonin 4 receptor

PMID:
27894797
DOI:
10.1016/j.brainres.2016.11.021
[Indexed for MEDLINE]

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