Gamma Frequency Inhibits the Secretion and Aggregation of Amyloid-β and Decreases the Phosphorylation of mTOR and Tau Proteins in vitro

Article type: Research Article

Authors: Yang, Yuan-Han^{a; b; c; d; 1} | Hsieh, Sun-Wung^{a; c; e; f; 1} | Chang, Hsi-Wen^g | Sung, Jia-Li^h | Chuu, Chih-Pinⁱ | Yen, Chen-Wen^{b; c; h; j; *} | Hour, Tzyh-Chyuan^{c; g; k; *}

Affiliations: [a] Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan | [b] School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan | [c] Neuroscience Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan | [d] Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan | [e] Department of Neurology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan | [f] Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan | [g] Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan | [h] Department of Mechanical and Electromechanical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan | [i] Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan | [j] Department of Physical Therapy, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan | [k] Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Correspondence: [*] Correspondence to: Tzyh-Chyuan Hour, Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Tel.: +886 7 312 1101 /Ext. 2138; E-mail:cliff@kmu.edu.tw and Chen-Wen Yen, Department of Mechanical and Electromechanical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan. No. 70, Lienhai Rd., Kaohsiung 804, Taiwan. Tel.: +886 7 525 2000 /Ext. 4232; E-mail:cmurobot@gmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Alzheimer’s disease (AD) was the main cause of dementia in an aging society; unfortunately, there is no effective treatment for AD now. Meditation has been reported to thicken the cerebral cortex, and gamma wave at a frequency of 40 hertz (Hz) was recorded during the meditation process from the brain. Previous study showed that non-invasive scintillation gamma frequency oscillation increased the space in recognition and memory of auditory cortex hippocampal gyrus in AD mice model. However, the AD-related molecular change by exposure of 40 Hz gamma frequency in brain cells was still unclear. Objective:We investigated the AD-related molecular change by exposure of 40 Hz gamma frequency in SH-SY5Y cells. Methods:We designed the light and sound generators at 40 Hz gamma frequency for this study. SH-SY5Y cells were exposed to sound or light of 40 Hz gamma frequency, respectively. The concentrations of amyloid-β40 (Aβ40) and amyloid-β42 (Aβ42) were quantified by enzyme-linked immunosorbent assay. The protein levels were examined by Western blotting. The aggregation of Aβ42 was examined by thioflavin T assay. Results:Our results showed that the secretion of Aβ, phosphorylation of AKT, mTOR, and tau, and aggregation of Aβ42 were significantly inhibited by 40 Hz gamma frequency in SH-SY5Y cells. The phosphorylation of 4E-BP1, downstream of mTOR, was induced by 40 Hz gamma frequency in SH-SY5Y cells. Conclusion:Our study showed 40 Hz gamma frequency involved in the inhibition of secretion and aggregation of Aβ and inhibition of p-Tau protein expression through the mTOR/4E-BP1/Tau signaling pathway.

Keywords: Alzheimer disease, amyloid-β, gamma frequency, mTOR, tau

DOI: 10.3233/JAD-220307

Journal: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 917-928, 2022