Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons

Youngjae Ryu, Takahiro Maekawa, Daisuke Yoshino, Naoyoshi Sakitani, Atsushi Takashima, Takenobu Inoue, Jun Suzurikawa, Jun Toyohara, Tetsuro Tago, Michiru Makuuchi, Naoki Fujita, Keisuke Sawada, Shuhei Murase, Masashi Watanave, Hirokazu Hirai, Takamasa Sakai, Yuki Yoshikawa, Toru Ogata, Masahiro Shinohara, Motoshi NagaoYasuhiro Sawada

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT2A receptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT2A receptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.

Original languageEnglish
Article number100874
JournaliScience
Volume23
Issue number2
DOIs
Publication statusPublished - 2020 Feb 21

Keywords

  • Biological Sciences
  • Cellular Neuroscience
  • Molecular Neuroscience
  • Neuroscience

ASJC Scopus subject areas

  • General

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