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1. Renal function is associated with 1-month and 1-year mortality in patients with ischemic stroke

Author

I-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Sheng-Feng Sung, Pai-Hao Huang, Jie-Yuan Li, Yu Sun, Cheng-Yu Wei, Li-Ming Lien, I-Ju Tsai, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyu, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Chih-Hao Chen, Hsin-Hsi Tsai, Han-Jung Chen, Kan Lu, Shih-Pin Hsu, Hung-Chang Kuo, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Meng-Tsang Hsieh, Po-Chao Liliang, Cheng-Loong Liang, Hao-Kuang Wang, Yu-Tun Tsai, Kuo-Wei Wang, Jui-Sheng Chen, Po-Yuan Chen, Yi-Ching Wang, Chih-Hung Chen, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Ruey-Tay Lin, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Huey-Juan Lin, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, An-Chih Chen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Wei-Lun Chang, Pai-Yi Chiu, Min-Hsien Hsu, Po-Chi Chan, Chau-Hsiung Pan, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Wei-Chieh Chang, Ta-Chang Lai, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Siu-Pak Lee, Ming-Hui Sun, Li-Ying Ke, Po-Lin Chen, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiunn-Tay Lee, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu- Hua Lai, Chun-I. Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Tsuey-Ru Chiang, Pin-Wen Liao, Mei-Ching Lee, Jen-Tse Chen, Sian-King Lie, Mu-Chien Sun, Pi-Ju Hsiao, Wei-Liang Chen, Ta-Cheng Chen, Chen-Shu Chang, Chien-Hsu Lai, Chieh-Sen Chuang, Yen-Yu Chen, Shinn-Kuang Lin, Yu-Chin Su, Jen-Lun Shiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Guei-Chiuan Chen, Po-Jen Hsu, Chun-Yuan Chang, I.-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I. Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau-Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Chao-Hsien Hung, Chia Fang Lee, Sheng-Kung Yang, Chih-Lin Chen, Wei Lin, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Lung Chan, Nai-Fang Chi, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E. Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Cheng-Yang Hsieh, Wei-Fen Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Kun-Chang Tsai, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Adult, Male, Stroke registry, medicine.medical_specialty, Time Factors, Adolescent, Taiwan, Renal function, 030204 cardiovascular system & hematology, Kidney, Risk Assessment, Brain Ischemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, In patient, Registries, Risk factor, Stroke, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Middle Aged, Prognosis, medicine.disease, Ischemic stroke, Cardiology, Female, Kidney Diseases, Cardiology and Cardiovascular Medicine, business, 1 year mortality, 030217 neurology & neurosurgery, Glomerular Filtration Rate
Abstract

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Published
2018
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2. Depression in Older Adults Among Community: The Role of Executive Function

Author

Ping-Keung Yip, Kaw-Chen Wang, Zai-Ting Yeh, and Yan-You Lu

Subjects
030214 geriatrics, business.industry, Stepwise regression analysis, Regression analysis, lcsh:Geriatrics, humanities, 030227 psychiatry, lcsh:RC952-954.6, 03 medical and health sciences, 0302 clinical medicine, Medicine, Elderly people, Verbal fluency test, Geriatric Depression Scale, Modified card sorting test, Geriatrics and Gerontology, business, Depression (differential diagnoses), Clinical psychology, Executive dysfunction
Abstract

Summary: Background: Although previous studies have proposed that elderly depression is associated with higher negative affect (NA) and lower positive affect (PA), the relationship between elderly depression and executive function remains controversial. Methods: Participants were recruited from the community and assessed using the Mini-Mental State Examination, the Geriatric Depression Scale, PA and NA tests, the Modified Card Sorting test (MCST), and a test of verbal fluency (VF). The participants were 319 middle-aged people (mean age = 58.05) and 276 elderly people (mean age = 74.41). The participants in each age group were then divided into a depression group and a control group according to their geriatric depression scale scores. Results: Compared to the middle-aged group, the elderly group displayed significantly poorer executive function. Compared to the elderly control group, the depressed elderly group displayed poorer executive function, but this phenomenon was not found in the middle-aged group. Stepwise regression analysis showed that the factors of depression were NA and low PA for both the middle-aged and elderly depression groups. However, executive function including MSCT and VF were non-significant variables in regression analysis. Conclusion: Executive dysfunction in elderly people with depression may be associated with the age effect. As people with depression age, their executive dysfunction becomes more pronounced. An elevated NA and lack of PA can explain the severity of depression, but executive function cannot explain depression in either middle-aged or elderly people. Keywords: aging, depression, executive function, affect

Published
2017
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3. Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients

Author

I.-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Shih-Pin Hsu, Chih-Hung Chen, Li-Ming Lien, Ruey-Tay Lin, An-Chih Chen, Huey-Juan Lin, Hsin-Yi Chi, Ta-Chang Lai, Yu Sun, Siu-Pak Lee, Sheng-Feng Sung, Po-Lin Chen, Jiunn-Tay Lee, Tsuey-Ru Chiang, Shinn-Kuang Lin, Chih-Hsin Muo, Henry Ma, Chi-Pang Wen, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyn, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Han-Jung Chen, Cheng-Sen Chang, Hung-Chang Kuo, Lian-Hui Lee, Huan-Wen Tsui, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Kun-Chang Tsai, Yen-Wen Chen, Kan Lu, Po-Chao Liliang, Yu-Tun Tsai, Cheng-Loong Liang, Kuo-Wei Wang, Hao-Kuang Wang, Jui-Sheng Chen, Po-Yuan Chen, Cien-Leong Chye, Wei-Jie Tzeng, Pei-Hua Wu, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Chou-Hsiung Pan, Po-Chi Chan, Min-Hsien Hsu, Wei-Lun Chang, Zhi-Zang Huang, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Ming-Hui Sun, Li-Ying Ke, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu-Hua Lai, Chun-I Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Mei-Ching Lee, Pai-Hao Huang, Sian-King Lie, Pin-Wen Liao, Jen-Tse Chen, Mu-Chien Sun, Tien-Pao Lai, Wei-Liang Chen, Yen-Chun Chen, Ta-Cheng Chen, Wen-Fu Wang, Kwo-Whei Lee, Chen-Shu Chang, Chien-Hsu Lai, Siao-Ya Shih, Chieh-Sen Chuang, Yen-Yu Chen, Chien-Min Chen, Yu-Chin Su, Cheng-Lun Hsiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Chun-Yuan Chang, I-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Pai-Yi Chiu, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau- Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Cheng-Yu Wei, Chao-Nan Yang, Chao-Hsien Hung, Ian Shih, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Nai-Fang Chi, Lung Chan, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Shi-Cheng Chen, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Chih-Hao Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Male, Stroke registry, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Taiwan, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Dialysis patients, Brain Ischemia, 03 medical and health sciences, chemistry.chemical_compound, Patient Admission, 0302 clinical medicine, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Registries, Serum cholesterol, Dialysis, Aged, Proportional Hazards Models, Aged, 80 and over, Cholesterol, business.industry, Mortality rate, Rehabilitation, Middle Aged, Prognosis, Stroke, chemistry, 30 day mortality, Ischemic stroke, Cardiology, Kidney Failure, Chronic, Female, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Published
2017
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4. The relationship between theory of mind and the executive functions: Evidence from patients with frontal lobe damage

Author

Chiao-Yu Lo, Zai-Ting Yeh, Kaw-Chen Wang, Ming-Dar Tsai, and Ming-Cheng Tsai

Subjects
Adult, Male, Planning, Adolescent, Theory of Mind, Neuropsychological Tests, 050105 experimental psychology, Developmental psychology, Executive Function, Young Adult, 03 medical and health sciences, Cognition, 0302 clinical medicine, Theory of mind, Developmental and Educational Psychology, Craniocerebral Trauma, Humans, 0501 psychology and cognitive sciences, 05 social sciences, Neuropsychology, Attentional control, Middle Aged, Executive functions, Frontal Lobe, Functional imaging, Affect, Neuropsychology and Physiological Psychology, Frontal lobe, Case-Control Studies, Female, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

"Theory of mind" (ToM) refers to the ability to predict others' thoughts, intentions, beliefs, and feelings. Evidence from neuropsychology and functional imaging indicates that ToM is a domain-specific or modular architecture; however, research in development psychology has suggested that ToM is the full development of the executive functions in individuals. Therefore, the relationship between ToM and the executive functions needs to be clarified. Since the frontal lobe plays a critical role in the abilities of ToM and the executive functions, patients with frontal lobe damage were recruited for the present study. Assessments of ToM and the executive functions were performed on 23 patients with frontal lobe damage and 20 healthy controls. When controlling for the executive functions, significant differences between the patient and normal groups were found in the affective component of ToM, but not in the cognitive component. The present study suggests that in various social situations, executing ToM abilities requires logical reasoning processes provided by the executive functions. However, the reasoning processes of affective ToM are independent of executive functions.

Published
2016
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5. Liu Jun Zi Tang—A Potential, Multi-Herbal Complementary Therapy for Chemotherapy-Induced Neurotoxicity

Author

Chun Tang Chiou, Kaw-Chen Wang, Chuen-Lin Huang, Sien-Hung Yang, Ying-Chen Yang, Nai Kuei Huang, and Yao-Haur Kuo

Subjects
0301 basic medicine, cisplatin, PGC-1α, Apoptosis, Mitochondrion, Pharmacology, Liu Jun Zi Tang, Catalysis, Article, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, Mice, 0302 clinical medicine, Neuroblastoma, Cell Line, Tumor, Coactivator, neurotoxicity, medicine, Gene silencing, Animals, Humans, Physical and Theoretical Chemistry, Receptor, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Cisplatin, Membrane Potential, Mitochondrial, business.industry, Organic Chemistry, Neurotoxicity, General Medicine, medicine.disease, mitochondria, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Computer Science Applications, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Hyperalgesia, Neurotoxicity Syndromes, business, 030217 neurology & neurosurgery, medicine.drug, Drugs, Chinese Herbal
Abstract

Liu Jun Zi Tang (LJZT) has been used to treat functional dyspepsia and depression, suggesting its effects on gastrointestinal and neurological functions. LJZT is currently used as a complementary therapy to attenuate cisplatin-induced side effects, such as dyspepsia. However, its effect on chemotherapy-induced neuropathic pain or neurotoxicity has rarely been studied. Thus, we explored potential mechanisms underlying LJZT protection against cisplatin-induced neurotoxicity. We observed that LJZT attenuated cisplatin-induced thermal hyperalgesia in mice and apoptosis in human neuroblastoma SH-SY5Y cells. Furthermore, it also attenuated cisplatin-induced cytosolic and mitochondrial free radical formation, reversed the cisplatin-induced decrease in mitochondrial membrane potential, and increased the release of mitochondrial pro-apoptotic factors. LJZT not only activated the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) promoter region, but also attenuated the cisplatin-induced reduction of PGC-1α expression. Silencing of the PGC-1α gene counteracted the protection of LJZT. Taken together, LJZT mediated, through anti-oxidative effect and mitochondrial function regulation, to prevent cisplatin-induced neurotoxicity.

Published
2018

6. Gastrodia elata alleviates mutant huntingtin aggregation through mitochondrial function and biogenesis mediation

Author

Ying-Chen Yang, Chun Tang Chiou, Yun-Lian Lin, Nai Kuei Huang, Kaw-Chen Wang, Chia-Hui Tan, and Chuen-Lin Huang

Subjects
0301 basic medicine, Huntingtin, Mutant, Pharmaceutical Science, Protein aggregation, Mitochondrion, CREB, PC12 Cells, 03 medical and health sciences, 0302 clinical medicine, Western blot, Drug Discovery, Coactivator, medicine, Animals, Humans, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Promoter Regions, Genetic, Pharmacology, Huntingtin Protein, Gastrodia, medicine.diagnostic_test, biology, Chemistry, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cell biology, Adenosine A2 Receptor Antagonists, Mitochondria, Rats, 030104 developmental biology, Huntington Disease, Neuroprotective Agents, Complementary and alternative medicine, biology.protein, Molecular Medicine, 030217 neurology & neurosurgery, Drugs, Chinese Herbal
Abstract

Background According to the Compendium of Materia Medica, Gastrodia elata (GE) Blume is a top-grade herbal medicine frequently used to treat dizziness, headaches, tetanus, and epilepsy, suggesting that it affects neurological functions. Although studies have supported its effects in preventing diverse neurodegenerations such as Huntington's disease (HD), its mechanisms require further investigation. Purpose To investigate the ability of the molecular mechanism of GE to prevent mutant huntingtin (mHTT) protein aggregation by focusing on mitochondrial function and biogenesis, which have been proposed as the therapeutic targets of HD. Study Design/Methods mHtt overexpression in pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A retardation assay was applied to measure protein aggregation during Htt expression. Cotransfection with transcriptional genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope. Western blot analysis was used to estimate protein expression under different drug treatments or when cotransfected with other related genes. Results Mutant, abnormal Htt overexpression resulted in significant protein aggregation in PC12 cells. GE dose-dependently attenuated mHTT aggregates and increased cyclic-AMP response element-binding protein (CREB) phosphorylation. Adenosine A2A-R receptor (A2A-R) antagonist counteracted these phenomena. CREB overexpression significantly attenuated mHTT aggregation. GE increased the promoter activity and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Furthermore, wild-type PGC-1α but not mutant PGC-1α overexpression attenuated mHTT aggregates. Conclusion GE attenuated mHtt aggregation by mediating mitochondrial function and biogenesis through the A2A-R/PKA/CREB/PGC-1α-dependent pathway.

Published
2017

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