吳芎歷 研究員

所屬單位

高雄院區生物醫學轉譯研究所

專長領域

環境對學習與記憶的影響
飲食對學習與記憶的影響
飲食對腸道菌相及中樞神經功能的影響

電子郵件信箱

klhwu@cgmh.org.tw

聯絡電話

(07) 731-7123 ext 8596

中樞神經因應外在環境的變動，彙整並調節個體內在的訊息以維持生理功能的恆常運作。飲食是個體獲得能量維持生理功能主要來源，過度飲食損害器官生理功能。我們的研究主題為探討高糖飲食影響學習記憶中樞，海馬廻，導致學習記憶能力缺失的致病機轉。並透過動物模式研究尋求臨床治療與預防最適宜的時機與策略。粒線體為細胞能量代謝的核心，因應細胞外的營養源濃度波動，維持細胞功能。因此粒線體品質控制與恆定維持受到多個機制調控，避免因粒線體失能造成細胞失能，甚至死亡。我們的研究著眼於粒線體功能的恆定與波動因應環境改變所扮演的角色，並將研究理念延伸至臨床應用，與臨床醫師合作探討兒童急性心臟衰竭以及慢性發炎引起腦中風的機轉與治療效益。

研究主題一

探討環境與高果糖飲食影響子代學習與記憶的機轉

經由懷孕及哺乳期餵食高糖飲食的動物模式，我們證實子代學習與記憶能力受損。由環境豐富化刺激，子代學習與記憶能力可回復正常。其中一個重要的因素為星狀膠細胞的能量代謝功能受抑制而限制星狀膠細胞-神經元代謝偶合效應，進而影響神經活性。

研究主題二

探討環境與高果糖飲食影響個體學習與記憶的機轉

我們證實經由餵食高果糖飲食的動物模式，造成個體學習與記憶能力受損。高果糖飲食習慣經由引起神經發炎，降低突觸可塑性以及抑制新生造成學習與記憶能力受損。其中，腸道菌相失衡扮演重要角色。

合作研究主題一

探討急性正腎上腺素上升影響兒童心肺功能的機轉及臨床用藥效益的評估

我們與兒童內科林宜君副部長合作以急性正腎上腺素 (norepinephrine, NE) 上升的動物模式，模擬腸病毒 71 型引起急性心臟衰竭的症狀，研究心肺細胞因應急性正腎上腺素上升，改變細胞分子的生理功能並影響臨床用藥的反應用以提高治療成效。

合作研究主題二

探討發炎影響腦血管自主調控的機轉及對腦中風預後的影響

我們與腦血管科傅睦惠醫師合作以腦中風的動物模式，探索腦中風影響腦血管自主調控，改變神經生理功能的機轉並發展新興療法提高治療效益。

Selected recent publications (Pubmed Search)
 († Contributed equally to the article; * Correspondence author of the article)

1. Weng JR, Wu CW, Chen YC, Fu MF, Tain YL, Hung CY, Chen IC, Lee CW, Wu KLH*. Fructose milieu undermines the therapeutic effect of Tribulus terrestris Extract on neuroblastoma cell line via maintaining mitochondrial function. (2022) Environmental Toxicology. doi: 10.1002/tox.23632.
2. Lee WC, Wu KLH, Tain YL, Leu S, Cheng YT, Chan JYH*. Impaired insulin signaling at the bladder mucosa facilitates metabolic syndrome-associated bladder overactivity in rats with maternal and post-weaning fructose exposure. (2022) J Formos Med Assoc. Oct 4:S0929-6646(22)00363-1. doi: 10.1016/j.jfma.2022.09.013.
3. Lin IC*, Wu CW, Lin YJ, Lo MH, Hsieh KS, Chan JYH and Wu KLH*. Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats. (2022) Pediatric Research. doi: 10.1038/s41390-022-01964-6.
4. Chang HH, Lin IC, Wu CW, Hung CY, Liu WC, Wu CY, Cheng CL*, Wu KLH*. High fructose induced osteogenic differentiation of human valve interstitial cells via activating PI3K/AKT/mitochondria signaling. (2022) Biomedical Journal. 45(3):491-503.
5. Huang HM, Wu CW, Chen IC, Lee YC, Huang YS, Hung CY, Wu KLH*. Maternal high fructose diet induced early onset retinopathy via the suppression of synaptic plasticity mediated by the mitochondrial dysfunction. (2021) Am J Physiol Endocrinol Metab. 320(6):E1173-E1182.
6. Liu WC, Wu CW, Hung PL, Chan JYH, Tain YL, Fu MH, Chen LW, Liang CK, Hung CY, Yu HR, Chen IC, Wu KLH*. (2020) Environmental stimulation counteracts the suppressive effects of maternal high fructose diet on cell proliferation and neuronal differentiation in the dentate gyrus of adult female offspring via histone deacetylase 4. Int J Environ Res Public Health. 81:108378.
7. Chao YM, Wu KLH, Tsai PC, Tain YL, Leu S, Lee WC, Chan JYH*. (2020) Anomalous AMPK-regulated Angiotensin AT 1 R Expression and SIRT1-mediated Mitochondrial Biogenesis at RVLM in Hypertension Programming of Offspring to Maternal High Fructose Exposure. J Biomed Sci. 27(1):68.
8. Liu WC, Wu CW, Fu MH, Tain YL, Liang CK, Hung CY, Chen IC, Lee YC, Wu CY and Wu KLH*. (2020) Maternal high fructose-induced hippocampal neuroinflammation in the adult female offspring via PPARg-NF-kB signaling. J Nutr Biochem 81:108378.
9. Fu MH, Chen IC, Lee CH, Wu CW, Lee YC, Kung YC, Hung CY, Wu KLH*. (2019) Anti-neuroinflammation ameliorates systemic inflammation-induced mitochondrial DNA impairment in the nucleus of the solitary tract and cardiovascular reflex dysfunction. J Neuroinflammation. 16(1):224.
10. Lin IC, Wu CW, Tain YL, Chen IC, Hung CY, Wu KLH*. (2019) High fructose diet-induced early mortality via autophagy factors accumulation in the rostral ventrolateral medulla is ameliorated by Pioglitazone. J Nutr Biochem. 69:87-97.
11. Suwanjang W*, Wu KLH, Prachayasittikul S, Chetsawang B, Charngkaew K. (2019) Mitochondrial Dynamics Impairment in Dexamethasone-Treated Neuronal Cells. Neurochem Res. 44:1567-1581.
12. Wu CW, Hung CY, Hirase H, Tain YL, Lee WC, Chan JYH, Fu MH, Chen LW, Liu WC, Liang CK, Ho YH, Kung YC, Leu S, Wu KLH*. (2019) Pioglitazone reversed the fructose-programmed astrocytic glycolysis and oxidative phosphorylation of female rat offspring. Am J Physiol Endocrinol Metab. 16:E622-E634.
13. Fu MH, Wu CW, Lee YC, Hung CY, Chen IC, Wu KLH*. (2018) Nrf2 activation attenuates the early suppression of mitochondrial respiration due to the alpha-synuclein overexpression. Biomedical Journal. 41(3):169-183.
14. Liu WC, Wu CW, Tain YL, Fu MH, Hung CY, Chen IC, Chen LW, Wu KLH*. (2018) Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis. BBA – Molecular Basis of Disease. 1864:274-285.
15. Wu KLH*, Wu CW, Tain YL, Chao YM, Hung CY, Tsai PC, Wang WS, Shih CD*. (2017) Effects of high fructose intake on the development of hypertension in the spontaneously hypertensive rats: the role of AT1R/gp91PHOX signaling in the rostral ventrolateral medulla. J Nutr Biochem. 41:73-83.

洪純瑛

陳怡君

李育綺

Education

Honors

Research Experiences

• Aug, 2021-

Name of Institute:

Institute for Translational Research in Biomedine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.

Job Title: Professor (Hospital)/ Associate Professor (College)

• Aug, 2015-July, 2021

Name of Institute:

Institute for Translational Research in Biomedine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.

Job Title: Associate Professor (Hospital)/ Assistant Professor (College)

• June, 2011-July, 2015

Name of Institute:

Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.

Job Title: Assistant Professor

• September, 2008- May, 2011

Name of Institute:

Neural Structure & Function Research Laboratory, Department of Medical Education and Research,

Veterans General Hospital-Kaohsiung.

Job Title: postdoctoral fellow

Supervisor: Prof. Julie Y. H. Chan

• September, 2007-2008

Name of Institute:

Center for Neuroscience, National Sun Yat-sen University.

Job Title: postdoctoral fellow

Supervisor: Prof. Samuel H. H. Chan

• September, 2002-2007

Name of Institute:

1. The Graduate Institute of Medicine, Kaohsiung Medical University.
2. Neural Structure & Function Research Laboratory, Department of Medical Education and Research, Veterans General Hospital-Kaohsiung.

Job Title: Ph D student

Supervisor: Prof. Julie Y. H. Chan and Prof. Chin Hsu

• September, 1999 –2002

Name of Institute:

Neural Structure & Function Research Laboratory, Department of Medical Education and Research,
Veterans General Hospital-Kaohsiung.

Job Title: Research technologist

Supervisor: Prof. Julie Y. H. Chan

Project

Protective role of brain-derived neurotrophic factor in neuronal cell death of pontine reticular formation after spinal cord injury.

• March, 1993 –1997

Name of Institute:
Molecular Biology & Veterinary Virology Laboratory,
College of Veterinary Medicine,
National Chung-Hsing University.

Job Title: Research technologist

Supervisor: Dr. Tien-Jye Chang

Project

1. Study of early genes on pseudorabies virus expression, gene regulation, and biological functions.
2. Construction of a gene-deleted mutant or a replication-deficient virus as an expression vector for foreign genes or a live virus vaccine.