@article{098f33470421404b9e14be09c7dbbaf0,
title = "Mechanical Regulation Underlies Effects of Exercise on Serotonin-Induced Signaling in the Prefrontal Cortex Neurons",
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.",
keywords = "Biological Sciences, Cellular Neuroscience, Molecular Neuroscience, Neuroscience",
author = "Youngjae Ryu and Takahiro Maekawa and Daisuke Yoshino and Naoyoshi Sakitani and Atsushi Takashima and Takenobu Inoue and Jun Suzurikawa and Jun Toyohara and Tetsuro Tago and Michiru Makuuchi and Naoki Fujita and Keisuke Sawada and Shuhei Murase and Masashi Watanave and Hirokazu Hirai and Takamasa Sakai and Yuki Yoshikawa and Toru Ogata and Masahiro Shinohara and Motoshi Nagao and Yasuhiro Sawada",
note = "Funding Information: We thank Dr. Y. Ikegaya and Ms. R. Kono (The University of Tokyo) for their technical support to primary neuron culture. This work was in part supported by Intramural Research Fund from the Japanese Ministry of Health, Labour and Welfare; Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to T.O. and Y.S.); and MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015-2019 from the Japanese Ministry of Education, Culture, Sports, Science and Technology ( S1511017 ). Funding Information: We thank Dr. Y. Ikegaya and Ms. R. Kono (The University of Tokyo) for their technical support to primary neuron culture. This work was in part supported by Intramural Research Fund from the Japanese Ministry of Health, Labour and Welfare; Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to T.O. and Y.S.); and MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015-2019 from the Japanese Ministry of Education, Culture, Sports, Science and Technology (S1511017). Y.R. proposed the initial idea related to HTR analysis in this project. Y.S. conceived and designed the study, supervised and led the project, and wrote the manuscript. Y.R. and T.M. conducted most of the experiments. D.Y. helped in vitro FSS experiments and carried out simulative calculation of in vivo fluid shear stress. N.S. conducted the experiments using primary neurons and ?CT analysis. T.M. A.T. J.S. T.I. and S.M. contributed to the design and construction of the machine for PHM. J.T. and M.M. contributed to the acquisition and the analysis of MRI data, respectively. T.S. and Y.Y. developed and provided the PEG hydrogel system. M.N. N.F. K.S. S.W. T.T. M.W. H.H. T.O. and M.S. provided technical, advisory and financial support. Y.R. T.M. A.T. T.I. J.S. S.M. T.O. and Y.S. joined the application for a patent related to this work, which has been granted in Japan (JP6592834) and filed internationally (US16/616,935; EP18806753.2; CN201880033284.0; IN201927048891), as inventors. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = feb,
day = "21",
doi = "10.1016/j.isci.2020.100874",
language = "English",
volume = "23",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "2",
}