Browsing by Author "Chen, Yu-Hsin"

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Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia
(2015-06-15)
Tsai, Wen-Chin
;
Lu, Yen-Yu
;
Chen, Yao-Chang
;
Chang, Chien-Jung
;
Kao, Yu-Hsun
Background: Sex hormones and calcium (Ca2+) regulation play roles in the pathophysiology of ventricular tachycardia from right ventricular outflow tract (RVOT). The purpose of this study was to evaluate whether androgen receptor knockout (ARKO) can increase RVOT arrhythmogenesis through modulating RVOT electrophysiology and Ca2+ homeostasis. Methods: Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10 months) before and after caffeine (1 mM), isoproterenol (1 mu M), adenosine (10 mu M) and flecainide (5 mu M) administration. The Fluo-3 fluorescence Ca2+ imaging with confocal microscopy and western blots were used to investigate intracellular Ca2+ (Ca-i(2+)) transients, Ca2+ sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. Results: We found that ARKO RVOTs (n = 13) had longer AP duration, faster burst firing (5.4 +/- 0.7 vs. 3.4 +/- 0.7 Hz, P < 0.05), and higher incidence of early afterdepolarizations (82% vs. 8%, P < 0.001) than WT RVOTs (n = 11). Adenosine and flecainide can suppress caffeine-or isoproterenol-induced spontaneous rates and burst firing in WT RVOTs, but not in ARKO RVOTs. ARKO RVOT myocytes had a higher frequency (7.7 +/- 2.8 vs. 1.3 +/- 0.4 spark/mm/s, P < 0.05) and incidence (89% vs. 47%, P < 0.05) of Ca2+ sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO andWT RVOT myocytes exhibit similar Ca-i(2+) transients and SR Ca2+ content, and less expression of calsequestrin. Conclusions: ARKO changes RVOT electrophysiology and Ca2+ homeostasis with increased ventricular arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Development of a Multisite, Closed-loop Neuromodulator for the Theranosis of Neural Degenerative Diseases
(2018-01-01)
Chen, Hsin
;
Chang, Yen-Chung
;
Yeh, Shih-Rung
;
Hsieh, Chih-Cheng
;
Tang, Kea-Tiong
Stimulating specific brain regions has been found useful for treating neural disorders, such as the Parkinson's disease, epilepsy, depression, etc. However, how electrical stimulation modulates neural activities remains not fully understood. As animal models provide the advantage of recording and stimulating different disease-related regions simultaneously, this paper introduces the latest development of a multisite, closed-loop-controlled microsystem for investigating novel treatments on neural degenerative diseases with freely-moving rats. The algorithms for recognizing pathological neural activities automatically are also developed and realized in hardware, so as to control the stimulation in a closed loop and in real time. The pilot studies on the efficacy of treating the Parkinson's disease with closed-loop-controlled stimulation will be presented and discussed. Finally, the feasibility of modelling and probing how neural dynamics and connectivity are modulated by stimulation will be an important topic for future research.