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Dietary Linoleic Acid Targets Skeletal Muscle to Impact Energy Metabolism (P08-124-19)

Current Developments in Nutrition 2019年第SUPPL 1期3卷 3131213-3131213页

作者： Snoke, Deena Hsuan-Hsiao, Yung Cole, Rachel Pedersen, Theresa Newman, John Borkowski, Kamil Banh, Taylor Angelotti, Austin Schnell, Patrick Belury, Martha OSU Interdisciplinary PhD Program in Nutrition The Ohio State University OSU Interdisciplinary PhD Program in Nutrition The Ohio State University Advanced Analytics USDA-Western Human Nutrition Research Center UC Davis Department of Human Sciences the Ohio State University Division of Biostatistics College of Public Health The Ohio State University

AbstractObjectivesInvestigate the impact of dietary linoleic acid (LA) on whole-body energy metabolism, fatty acid uptake, oxylipin metabolites, and energy production machinery in skeletal muscle. MethodsMice were fed modified AIN-93 M diets containing 6% wt of LA or palmitic acid (PA) for 5 weeks. To address energy balance, grip strength, blood glucose, and body composition were measured weekly and indirect calorimetry was performed after 4.5 weeks of diet. To address skeletal muscle architecture, cross-sectional area was quantified in quadriceps. To determine the effect of LA diet on skeletal muscle lipids, fatty acid composition was measured in quadriceps using GC. Targeted lipidomics using LC-MS/MS was utilized to measure LA-derived oxylipins in mitochondria isolated from gastrocnemius. ResultsNo difference in food intake, body weight, blood glucose, or body composition were observed between diet groups. Mice fed the LA diet exhibited higher heat production and lower respiratory exchange ratio, independent of ambulatory activity compared to mice fed the PA diet. Cross sectional area analysis in quadriceps muscle revealed that mice fed the LA diet had smaller muscle fibers compared to mice fed the PA diet. The LA diet increased LA level in quadriceps. Using hierarchal cluster analysis, we identified several unique patterns of oxylipins that impact insulin sensitivity and may be associated with increased mitochondrial capacity. Mice fed the LA diet exhibited a three-fold increase of oxylipin metabolites 9- and 13-HODE, and 12,13-diHOME. ConclusionsMice fed a diet fortified in LA have increased LA in skeletal muscle, changes to skeletal muscle architecture, favorable changes to whole body energy metabolism, and increases in LA-derived oxylipins in skeletal muscle mitochondria. Our discovery that LA generates 9-HODE and 13-HODE in muscle mitochondria suggests that downstream pathways, including PPARg transactivation, may be linked with effects on muscle energy metab

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Identification and characterization of the lncRNA signature associated with overall survival in patients with neuroblastoma

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SCIENTIFIC REPORTS 2019年第1期9卷 5125-5125页

作者： Sathipati, Srinivasulu Yerukala Sahu, Divya Huang, Hsuan-Cheng Lin, Yenching Ho, Shinn-Ying Natl Chiao Tung Univ Inst Bioinformat & Syst Biol Hsinchu Taiwan Natl Yang Ming Univ Inst Biomed Informat Ctr Syst & Synthet Biol Taipei Taiwan Acad Sinica Taiwan Int Grad Program Inst Informat Sci Bioinformat Program Taipei Taiwan Natl Chiao Tung Univ Interdisciplinary Neurosci PhD Program Hsinchu Taiwan Natl Chiao Tung Univ Dept Biol Sci & Technol Hsinchu Taiwan Natl Chiao Tung Univ Ctr Intelligent Drug Syst & Smart Biodevices IDS2 Hsinchu Taiwan

Neuroblastoma (NB) is a commonly occurring cancer among infants and young children. Recently, long non-coding RNAs (lncRNAs) have been using as prognostic biomarkers for therapeutics and interventions in various cancers. Considering the poor survival of NB, the lncRNA-based therapeutic strategies must be improved. This work proposes an overall survival time estimator called SVR-NB to identify the lncRNA signature that is associated with the overall survival of patients with NB. SVR-NB is an optimized support vector regression (SVR)-based method that uses an inheritable bi-objective combinatorial genetic algorithm for feature selection. The dataset of 231 NB patients that contains overall survival information and expression profiles of 783 lncRNAs was used to design and evaluate SVR-NB from the database of gene expression omnibus accession GSE62564. SVR-NB identified a signature of 35 lncRNAs and achieved a mean squared correlation coefficient of 0.85 and a mean absolute error of 0.56 year between the actual and estimated overall survival time using 10-fold cross-validation. Further, we ranked and characterized the 35 lncRNAs according to their contribution towards the estimation accuracy. Functional annotations and co-expression gene analysis of LOC440896, LINC00632, and IGF2-AS revealed the association of co-expressed genes in Kyoto Encyclopedia of Genes and Genomes pathways.

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Erythrocyte Long Chain Omega 3 Fatty Acids Are Associated with Higher Lean Mass in Postmenopausal Women Newly Diagnosed with Breast Cancer (P05-024-19).

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Current developments in nutrition 2019年第SUPPL 1期3卷 nzz030.P05-024-19-nzz030.P05-024-19页

作者： Martha Belury Rachel Cole Rebecca Andridge Qing Xie Ashleigh Keiter Janice KIecolt-Glaser The Ohio State University. OSU Interdisciplinary PhD Program in Nutrition The Ohio State University. Biostatistics The Ohio State University.

UNASSIGNED:Cancer contributes to adverse changes in body composition that may increase risk of cardiometabolic diseases. Skeletal muscle is a main driver of cardiometabolic health. We hypothesize that higher intake of long chain omega-3 polyunsaturated fatty acids (LCn3PUFAs) is associated with muscle health. This study evaluates whether LCn3PUFA exposure assessed in diet and in blood is associated with markers of muscle health in women with breast cancer.;UNASSIGNED:This is a cross-sectional analysis evaluating LCn3PUFA exposure and markers of muscle health in women ( = 150) prior to treatment for breast cancer. Exposure to LCn3PUFAs was assessed by a diet history questionnaire (DHQ), a question specifically about supplement usage and biomarker of LCn3PUFAs in red blood cells (RBC). Body composition were measured at the same visit using dual x-ray absorptiometry. Linear regression models were used to test for associations.;UNASSIGNED:13% ( = 19) of women reported using fish oil supplements (e.g., Supplement Users) and had significantly higher levels of RBC LCn3PUFAs than Supplement Non-users. In Supplement Non-users, there was a positive association between reported dietary exposure by DHQ and RBC LCn3PUFA levels. The n3 index (e.g., sum of RBC EPA + DHA) and DHA (22:6n3) were positively associated with appendicular lean mass/BMI. There were no significant correlations between RBC LCn3PUFAs with grip strength and or other measurements of body composition.;UNASSIGNED:As a biomarker of intake, RBC LCn3PUFAs are positively associated with appendicular lean mass, a measure of skeletal muscle mass. A future study should prospectively evaluate whether higher LCn3PUFA exposure (as measured in blood) is associated with maintaining better muscle health during and following cancer treatment.;UNASSIGNED:Funding was provided by the National Cattleman's Beef Association, NIH (JKG) CA186720, Ohio Agriculture Research and Development Center and the Carol S. Kennedy Professorship.

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Telenursing and Nurse-Patient Communication Within Fertility, Inc.

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JOURNAL OF HOLISTIC NURSING 2018年第1期36卷 38-53页

作者： Johnson, Bethany Quinlan, Margaret M. Marsh, Jaclyn S. Univ North Carolina Charlotte Commun Studies Charlotte NC USA Univ North Carolina Charlotte Womens & Gender Studies Charlotte NC USA Univ North Carolina Charlotte Commun Charlotte NC USA Univ North Carolina Charlotte Hlth Psychol Interdisciplinary PhD Program Charlotte NC USA Univ Nebraska Lincoln Family Commun Studies Lincoln NE USA

The purpose of this study is to examine patient perceptions of practitioner-patient communication in reproductive endocrinology and infertility (REI) practices. During this study, we uncovered the importance of telenursing for nurse-patient communication during REI treatment. Telenursing, which is defined as the use of wireless technology for out-of-office communication, is the basis for out-of-office communication. We examined participants' conceptualization of supportive and unsupportive communication, through the lens of biomedicalization theory. After conducting 23 interviews, we conclude that telenursing is integral to providing holistic nursing care during treatment at REI practices. We discuss efficient and effective uses of telenursing and patients' positive perceptions telenursing and assess telenursing as both an embrace of and form of resistance to biomedicalization within Fertility, Inc. Theoretical and practical implications are offered, including suggestions for increasing patient access to telenursing while protecting REI nurses from burnout.

关键词： biomedicalization telenursing supportive communication infertility nursing wireless technology Fertility Inc.

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New Insights on Cultural Patterns of Suicide in the United States: The Role of Honor Culture

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CROSS-CULTURAL RESEARCH 2017年第5期51卷 521-548页

作者： Crowder, Marisa K. Kemmelmeier, Markus Univ Nevada Interdisciplinary Social Psychol PhD Program Mail Stop 1300 Reno NV 89557 USA Univ Nevada Dept Sociol Reno NV 89557 USA

Cultural differences in suicide can be indicative of varying social pressures placed on individuals. High suicide rates in U.S. honor cultures have been proposed to reflect pressures associated with maintaining one's reputation. We extend this argument by highlighting that honor concerns differentially impact individuals based on gender, ethnicity, and age. Controlling for relevant confounds, we show that suicide rates were highest among older European American men from honor cultures, presumably because aging may render these men less capable of conforming to cultural ideals of masculinity. We discuss the need for process-focused and subgroup analyses when examining the effects of culture on suicide.

关键词： suicide honor culture ethnicity gender aging

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Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransduction

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SCIENTIFIC REPORTS 2019年第1期9卷 9086-9086页

作者： Gerardo, Heloisa Lima, Ana Carvalho, Joao Ramos, Joao R. D. Couceiro, Sofia Travasso, Rui D. M. das Neves, Ricardo Pires Graos, Mario Univ Coimbra CNC Ctr Neurosci & Cell Biol UC Biotech BldgBiocant Pk Cantanhede Portugal Univ Nova Lisboa Fac Sci & Technol Portugal PhD Program MIT Caparica Portugal Univ Coimbra Ctr Fis Dept Phys CFisUC Coimbra Portugal Max Planck Inst Dynam & Self Org Gottingen Germany Stemlab SA Crioestaminal Biocant Pk Cantanhede Portugal Univ Coimbra Inst Interdisciplinary Res Coimbra Portugal Technol Transfer Assoc Biocant Cantanhede Portugal

Biophysical cues influence many aspects of cell behavior. Stiffness of the extracellular matrix is probed by cells and transduced into biochemical signals through mechanotransduction protein networks, strongly influencing stem cell behavior. Cellular stemness is intimately related with mechanical properties of the cell, like intracellular contractility and stiffness, which in turn are influenced by the microenvironment. Pluripotency is associated with soft and low-contractility cells. Hence, we postulated that soft cell culture substrates, presumably inducing low cellular contractility and stiffness, increase the reprogramming efficiency of mesenchymal stem/stromal cells (MSCs) into induced pluripotent stem cells (iPSCs). We demonstrate that soft substrates (1.5 or 15 kPa polydimethylsiloxane - PDMS) caused modulation of several cellular features of MSCs into a phenotype closer to pluripotent stem cells (PSCs). MSCs cultured on soft substrates presented more relaxed nuclei, lower maturation of focal adhesions and F-actin assembling, more euchromatic and less heterochromatic nuclear DNA regions, and increased expression of pluripotency-related genes. These changes correlate with the reprogramming of MSCs, with a positive impact on the kinetics, robustness of colony formation and reprogramming efficiency. Additionally, substrate stiffness influences several phenotypic features of iPS cells and colonies, and data indicates that soft substrates favor full iPSC reprogramming.

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2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease--- Part I

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ACTA CARDIOLOGICA SINICA 2024年第5期40卷 479-543页

作者： Chao, Ting-Hsing Lin, Tsung-Hsien Cheng, Cheng-, I Wu, Yen-Wen Ueng, Kwo-Chang Wu, Yih-Jer Lin, Wei-Wen Leu, Hsing-Ban Cheng, Hao-Min Huang, Chin-Chou Wu, Chih-Cheng Lin, Chao-Feng Chang, Wei-Ting Pan, Wen-Han Chen, Pey-Rong Ting, Ke-Hsin Su, Chun-Hung Chu, Chih-Sheng Chien, Kuo-Liong Yen, Hsueh-Wei Wang, Yu-Chen Su, Ta-Chen Liu, Pang-Yen Chang, Hsien-Yuan Chen, Po-Wei Jimmy, Jyh-Ming Juang, Jyh-Ming Jimmy Lu, Ya-Wen Lin, Po-Lin Wang, Chao-Ping Ko, Yu-Shien Chiang, Chern-En Hou, Charles Jia-Yin Wang, Tzung-Dau Lin, Yen-Hung Huang, Po-Hsun Chen, Wen-Jone Natl Cheng Kung Univ Natl Cheng Kung Univ Hosp Coll Med Dept Internal Med Tainan 704302 Taiwan Chung Shan Med Univ Hosp Dept Internal Med Div Cardiol Taichung Taiwan Chung Shan Med Univ Sch Med Taichung Taiwan Kaohsiung Med Univ Hosp Dept Internal Med Div Cardiol Kaohsiung Taiwan Kaohsiung Med Univ Grad Inst Med Coll Med Fac Med Kaohsiung Taiwan Kaohsiung Chang Gung Mem Hosp Dept Internal Med Div Cardiol Kaohsiung Taiwan ChangGung Univ Coll Med Sch Med Taoyuan Taiwan Far Eastern Mem Hosp Cardiovasc Med Ctr Div Cardiol New Taipei City Taiwan Natl Yang Ming Chiao Tung Univ Sch Med Taipei Taiwan Yuan Ze Univ Grad Inst Med Taoyuan Taiwan MacKay Med Coll Inst Biomed Sci Dept Med New Taipei City Taiwan MacKay Mem Hosp Cardiovasc Ctr Dept Internal Med Taipei Taiwan Taichung Vet Gen Hosp Cardiovasc Ctr Taichung Taiwan Natl Yang Ming Chiao Tung Univ Cardiovasc Res Ctr Hsinchu Taiwan Healthcare & Management Ctr Taipei Taiwan Taipei Vet Gen Hosp Dept Med Div Cardiol Taipei Taiwan Natl Yang Ming Chiao Tung Univ Coll Med PhD Program Interdisciplinary Med PIM Hsinchu Taiwan Taipei Vet Gen Hosp Div Fac Dev Ctr Evidence Based Med Taipei Taiwan Inst Publ Hlth Hsinchu Taiwan Natl Yang Ming Chiao Tung Univ Inst Hlth & Welf Policy Coll Med Hsinchu Taiwan Natl Yang Ming Chiao Tung Univ Inst Pharmacol Taipei Taiwan Natl Taiwan Univ Hosp Ctr Qual Management Hsinchu Branch Hsinchu Taiwan Natl Taiwan Univ Coll Med Taipei Taiwan Natl Tsing Hua Univ Inst Biomed Engn Hsinchu Taiwan Natl Hlth Res Inst Inst Cellular & Syst Med Zhunan Taiwan MacKay Med Coll Dept Med New Taipei City Taiwan MacKay Mem Hosp Dept Cardiol Taipei Taiwan Natl Sun Yat Sen Univ Coll Med Sch Med Doctoral Program Clin & Expt Med Kaohsiung Taiwan Natl Sun Yat Sen Univ Ctr Excellence Metab Associated Fatty Liver Dis Kaohsiung Taiwan Chi Mei Med Ctr Dept Internal Med Div Cardiol Tainan Taiwan Acad Sinica Inst Biomed Sci Taipei Taiwan Natl Hlth Res Inst Inst Populat

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: "ABC(2)D(2)EFG-I'M-2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

关键词： Atherosclerotic cardiovascular disease Guidelines Primary prevention

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Pathophysiology and blood pressure measurements of hypertension in the elderly

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Journal of the Formosan Medical Association 2025年

作者： Chen, Fan-Yu Lee, Chun-Wei Chen, Yu-Jen Lin, Yen-Hung Yeh, Chih-Fan Lin, Chih-Ching Cheng, Hao-Min Division of Nephrology Department of Medicine Taipei Veterans General Hospital Taipei Taiwan School of Medicine College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Institute of Public Health and Community Medicine Research Center National Yang Ming Chiao Tung University College of Medicine Taipei Taiwan Cardiovascular Division Department of Internal Medicine MacKay Memorial Hospital MacKay Medical College New Taipei City Taiwan MacKay Junior College of Medicine Nursing and Management Taipei Taiwan Department of Cardiology Taipei Municipal Wanfang Hospital Taipei Taiwan Primary Aldosteronism Center at National Taiwan University Hospital Taipei Taiwan Division of Cardiology Department of Internal Medicine and Cardiovascular Center National Taiwan University Hospital Taipei Taiwan Department of Medical Education Taipei Veterans General Hospital Taipei Taiwan Department of Medicine National Yang Ming Chiao Tung University College of Medicine Taipei Taiwan Center for Evidence-Based Medicine Taipei Veterans General Hospital Taipei Taiwan PhD Program of Interdisciplinary Medicine (PIM) National Yang Ming Chiao Tung University College of Medicine Taipei Taiwan

Hypertension is a serious concern among the elderly, posing health risks and treatment challenges. In the first part of this review, we explore the pathophysiological mechanisms linking hypertension and aging, focusing on physiological changes such as arterial stiffening, in autonomic nervous system dysfunction, disruption of the renin-angiotensin-aldosterone system, aging-induced alterations in renal function, and the impact of salt-sensitive hypertension. The mnemonic “King/A+++/Hermès” aids in recalling the pathophysiology of aging-related hypertension. Accurate blood pressure measurements are important to determine the prognosis and treatment in the elderly;however, obtaining reliable measurement data in this population is not always easy, as changes in cardiovascular structure and hemodynamics with aging may lead to increased blood pressure variability. In the second part of this review, we evaluate the effectiveness of blood pressure monitoring in older adults, emphasizing the importance of precise measurements. We also assess the efficacy of home and ambulatory monitoring, discuss orthostatic hypotension and orthostatic hypertension, outline challenges in measuring blood pressure in individuals with atrial fibrillation, and explore the impact of aging on measurement errors. We conclude that understanding the interplay between hypertension and aging, coupled with precise blood pressure monitoring strategies tailored for older adults, is essential for effective management and to improve overall cardiovascular health in the elderly population. © 2025 Formosan Medical Association

关键词： Aging Blood pressure measurements Hypertension Pathophysiology

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Investigation of natural phenanthrenes and the antiproliferative potential of juncusol in cervical cancer cell lines

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PHYTOMEDICINE 2019年 58卷 152770-000页

作者： Kuo, Ching-Ying Schelz, Zsuzsanna Toth, Barbara Vasas, Andrea Ocsovszki, Imre Chang, Fang-Rong Hohmann, Judit Zupko, Istvan Wang, Hui-Chun Kaohsiung Med Univ Coll Pharm Grad Inst Nat Prod Kaohsiung 80708 Taiwan Univ Szeged Fac Pharm Dept Pharmacodynam & Biopharm H-6720 Szeged Hungary Univ Szeged Fac Pharm Inst Pharmacognosy H-6720 Szeged Hungary Univ Szeged Fac Med Dept Biochem H-6720 Szeged Hungary Natl Sun Yat Sen Univ Dept Marine Biotechnol & Resources Kaohsiung 80424 Taiwan Univ Szeged Interdisciplinary Ctr Nat Prod H-6720 Szeged Hungary Kaohsiung Med Univ PhD Program Translat Med Coll Med Kaohsiung 80708 Taiwan Kaohsiung Med Univ PhD Program Toxicol Coll Pharm Kaohsiung 80708 Taiwan Kaohsiung Med Univ Hosp Dept Med Res Ctr Kaohsiung 80756 Taiwan Kaohsiung Med Univ Hosp Translat Res Ctr Kaohsiung 80756 Taiwan

Background: Phenanthrenes isolated from Juncus species possess different biological activities, including anti-proliferative and antimigratory effects. Purpose: In this study, nine phenanthrenes isolated from the roots of Juncus inflexus were investigated for their antiproliferative activity on several gynecological cancer cell lines, using non-cancerous cells as controls. Methods: Antiproliferative activities of the compounds were determined by means of MTT assay. Flow cytometry was used for cell cycle analysis and determination of mitotic cells. Activities of caspase-3, -8, and -9 were detected by colorimetric kits. Tubulin polymerization was followed by kinetic absorbance determination. Action on tumor cell migration was described using wound healing assay. Western blot assays were used to determine apoptosis-related factors at protein level. Results: Among the compounds tested, juncusol exhibited the most substantial antiproliferative effect against cervical cancer HeLa cells. It was also revealed that juncusol has a distinct growth inhibitory effect in cervical cancer cell lines of various HPV status: it was highly active in HPV type 18-positive HeLa cells, while it was inactive in HPV type 16-positive SiHa and CaSki cells. Cell cycle analysis showed an increase in G2/M and subG1 cell populations after juncusol treatment. Caspase-3, -8, and -9 were detected to be activated by juncusol in HeLa cells, indicating that juncusol induces apoptotic cell death. Moreover, juncusol inhibited tubulin polymerization, as well as EGFR activation, suggesting two possible additional mechanisms that may account for juncusol's inducing a G2/M-phase cell cycle arrest and inhibiting cell migration. Conclusion: These results suggest that juncusol is a potent antiproliferative agent against HPV-18 related cervical cancer and may be considered as a lead compound for the development of innovative anticancer agents.

关键词： Juncaceae Juncus inflexus Antiproliferative and antimigratory effects Cell cycle arrest Tubulin polymerization

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_D-Cycloserine Ameliorates Autism-Like Deficits by Removing GluA2-Containing AMPA Receptors in a Valproic Acid-Induced Rat Model

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MOLECULAR NEUROBIOLOGY 2018年第6期55卷 4811-4824页

作者： Wu, Han-Fang Chen, Po See Hsu, Ya-Ting Lee, Chi-Wei Wang, Tzu-Feng Chen, Yi-Ju Lin, Hui-Ching Natl Yang Ming Univ Sch Med Dept & Inst Physiol Taipei 11221 Taiwan Natl Cheng Kung Univ Natl Cheng Kung Univ Hosp Dept Psychiat Coll Med Tainan 70101 Taiwan Natl Cheng Kung Univ Addict Res Ctr Tainan 70101 Taiwan Natl Cheng Kung Univ Taiwan Int Grad Program Interdisciplinary Neurosc Taipei Taiwan Acad Sinica Taipei Taiwan Natl Yang Ming Univ Brain Res Ctr Taipei 11221 Taiwan Taipei Med Univ Coll Med Sci & Technol PhD Program Neural Regenerat Med Taipei 11031 Taiwan

Valproic acid (VPA)-exposed rat offspring have demonstrated autism spectrum disorder (ASD) phenotypes and impaired N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala. NMDAR partial agonist (D)-cycloserine (DCS) has been reported to act as a cognitive enhancer by increasing the NMDAR response to improve autistic-like phenotypes in animals. However, the mechanism of DCS in alleviating the ASD is still unknown. Using combined behavioral, electrophysiological, and molecular approaches, we found that DCS administration rescued social interaction deficits and anxiety/repetitive-like behaviors observed in VPA-exposed offspring. In the amygdala synapses, DCS treatment reversed the decreased paired pulse ratio (PPR) and the impaired NMDAR-dependent LTD, increased the frequency and amplitude of miniature excitatory post-synaptic currents (mEPSCs), and resulted in a higher dendritic spine density at the amygdala synapses in the VPA-exposed offspring. Moreover, we found that DCS facilitated the removal of GluA2-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (GluA2/AMPARs) by inducing NMDAR-dependent LTD in the VPA-exposed offspring. We further established that the effects of DCS treatment, including increased GluA2/AMPAR removal and rescues of impaired social behavior, were blocked by Tat-GluA2(3Y), a GluA2-derived peptide that disrupted regulation of AMPAR endocytosis. These results provided the first evidence that rescue of the ASD-like phenotype by DCS is mediated by the mechanism of GluA2/AMPAR removal in VPA-exposed rat offspring.

关键词： Autism spectrum disorder (D)-Cycloserine Long-termdepression NMDARs GluA2/AMPARs Valproic acid

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