Serotonin induces Arcadlin in hippocampal neurons.

Hidekazu Tanaka, Toshinori Sawano, Naoko Konishi, Risako Harada, Chiaki Takeuchi, Yuki Shin, Hiroko Sugiura, Jin Nakatani, Takahiro Fujimoto, Kanato Yamagata

Neuroscience letters 2020 Mar 16

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The monoamine hypothesis does not fully explain the delayed onset of recovery after antidepressant treatment or the mechanisms of recovery after electroconvulsive therapy (ECT). The common mechanism that operates both in ECT and monoaminergic treatment presumably involves molecules induced in both of these conditions. A spine density modulator, Arcadlin (Acad), the rat orthologue of human Protocadherin-8 (PCDH8) and of Xenopus and zebrafish Paraxial protocadherin (PAPC), is induced by both electroconvulsive seizure (ECS) and antidepressants; however, its cellular mechanism remains elusive. Here we confirm induction of Arcadlin upon stimulation of an N-methyl-d-aspartate (NMDA) receptor in cultured hippocampal neurons. Stimulation of an NMDA receptor also induced acute (20 min) and delayed (2 h) phosphorylation of the p38 mitogen-activated protein (MAP) kinase; the delayed phosphorylation was not obvious in Acad-/- neurons, suggesting that it depends on Arcadlin induction. Exposure of highly mature cultured hippocampal neurons to 1-10 μM serotonin for 4 h resulted in Arcadlin induction and p38 MAP kinase phosphorylation. Co-application of the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (APV) completely blocked Arcadlin induction and p38 MAP kinase phosphorylation. Finally, administration of antidepressant fluoxetine in mice for 16 days induced Arcadlin expression in the hippocampus. Our data indicate that the Arcadlin-p38 MAP kinase pathway is a candidate neural network modulator that is activated in hippocampal neurons under the dual regulation of serotonin and glutamate and, hence, may play a role in antidepressant therapies. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Hidekazu Tanaka, Toshinori Sawano, Naoko Konishi, Risako Harada, Chiaki Takeuchi, Yuki Shin, Hiroko Sugiura, Jin Nakatani, Takahiro Fujimoto, Kanato Yamagata. Serotonin induces Arcadlin in hippocampal neurons. Neuroscience letters. 2020 Mar 16;721:134783