跳到主要內容

臺灣博碩士論文加值系統

(3.229.142.104) 您好!臺灣時間:2021/07/27 08:19
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:彭偉豪
研究生(外文):Wei-Hao Peng
論文名稱:檳榔鹼對小鼠味蕾和斑馬魚胚胎體節的影響
論文名稱(外文):Effects of Arecoline on the Murine Taste Bud and the Embryonic Zebrafish Somite
指導教授:盧國賢盧國賢引用關係
指導教授(外文):Kuo-Shyan Lu
口試委員:周逸鵬鄭景暉周綉珠
口試委員(外文):Yat-Pang ChauJiiang-Huei JengHsiu-Chu Chou
口試日期:2014-07-14
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:解剖學暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:130
中文關鍵詞:檳榔鹼味蕾斑馬魚
外文關鍵詞:arecolinetaste budzebrafish
相關次數:
  • 被引用被引用:1
  • 點閱點閱:152
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
檳榔鹼 (arecoline)是檳榔 (betel quid) 中含量最多的生物鹼 (alkaloid),嚼食檳榔會引起口腔之發炎、疾病及癌症,對於懷孕婦女更會造成早產及胎兒發育不良、體重過低等問題。檳榔鹼或嚼食檳榔對口腔之影響,已有甚多之研究,但口腔中的味蕾,是味覺的感受器官,若味蕾受到影響,可能會引起味覺異常,但鮮有研究指出檳榔鹼對味蕾的影響,故本論文之第一部分是研究檳榔鹼對味蕾的影響。另外,雖有甚多以不同動物針對檳榔鹼對懷孕的影響進行研究,但均做長時間的檳榔鹼接觸;因此本論文之第二部分選用斑馬魚為實驗動物,作短時間的檳榔鹼接觸,以模擬孕婦懷孕初期接觸檳榔鹼的影響。
實驗一:味蕾 (taste bud) 位在口腔舌頭表面乳突下的味覺接受器,若味蕾受到影響就有可能會影響味覺,但鮮有研究指出檳榔鹼對味蕾的影響。
實驗一係將雄性小黑鼠(C57BL/6)分成接受檳榔鹼1、2、3、4週的實驗組以及未接受檳榔鹼的控制組。將檳榔鹼2 mg/kg 一天兩次以腹腔注射方式給予各組之實驗小鼠;觀察 (1) 輪廓狀味蕾外形、大小、數量和內含味蕾細胞數;(2) 味蕾細胞超微結構分析;(3) 免疫螢光染色分析味覺接受器 (T1R1、T1R2、T1R3和T2R)以及味覺相關蛋白 (α-gustducin, PLCβ2 和 SNAP25) 的表現;(4) 在動物飲用含1%蔗糖之飲水後,統計孤立束核和味覺皮質區c-fos的表現量;(5) 紀錄動物的體重、攝食和飲水以及雙瓶喜好度行為。另外,要了解檳榔鹼對味蕾細胞更替率的影響,在各組實驗小鼠接受設定的檳榔鹼後,將BrdU 50mg/kg以腹腔注射方式給予,標定味蕾新生細胞,(6)統計在接受檳榔鹼後,味蕾內第1、3、7和14天被BrdU標定細胞數;(7)並且以RP-PCR測定舌頭上皮cyclin B2、E2F1、p53和bax味蕾更替相關基因的表現量。
結果發現,實驗小鼠接受檳榔鹼後,(1)小鼠味蕾的數量、大小及內含味蕾細胞數不會改變;(2) 味蕾第二型細胞內之粒線體、內質網明顯腫脹,低密度不規則顆粒變多,雙環小泡和密心顆粒結構腫脹且不規則,自噬小體數量明顯增加;(3) 免疫螢光染色之味蕾切片顯示甜味接受器 (T1R2和T1R3)表現量減少;(4) 含1%蔗糖之飲水實驗結果,顯示孤立束核和味覺皮質區c-fos的表現量降低;(5) 減少食物的攝取量導致體重沒有增加,並改變對甜味覺的喜好度。另外,(6)減少輪廓狀味蕾新生細胞數並縮短新生味蕾細胞的存活週期;(7) cyclin B2、E2F1表現量隨接受檳榔鹼時間的延長而減少,p53和bax則相反隨接受時間的延長而上升。
本研究顯示,長時間接受檳榔鹼會影響味蕾的超微結構,並改變味覺辨識能力及味蕾新生週期,這些可能會導致味覺異常或營養不足,進而影響發育生長。
實驗二:近年來,利用不同動物模式的研究,證實檳榔鹼能造成胚胎發育遲緩,現有已知的研究結果亦證實,長時間接觸檳榔鹼的斑馬魚胚胎,其發育過程也會受到影響。本實驗亦選用斑馬魚作實驗動物,但做短時間的檳榔鹼接觸,以模擬嚼食檳榔婦女在懷孕初期未能警覺懷孕而短暫接觸檳榔鹼對胎兒發育的影響。
將斑馬魚的受精卵在受精後4小時 ( 4hpf,hours post fertilization)內將其分組,各組受精卵分別以0.001%、0.01%、0.02%、0.04%的檳榔鹼處理20小時,並於24、48、72、96、120 hpf收集其胚胎,記錄 (1) 胚胎存活與孵化率;(2) 觀察胚胎發育外形的變化;(3) 紀錄胚胎魚泳游功能;(4) 並利用免疫螢光染色及穿透式電子顯微鏡觀察骨骼肌生長情形;(5) 利用RT-PCR及JC-1的方式釐清骨骼肌內的粒線體是否受到影響。
結果顯示,當斑馬魚胚胎接觸之檳榔鹼濃度提升時,各組斑馬魚之存活率、孵化率降低,外形明顯異常、體長縮短,且運動功能游泳距離縮短;免疫螢光染色可見體節(somite)內原本緻密排列的骨骼肌纖維,隨著接觸之檳榔鹼濃度的上升而顯得越不整齊;超微結構的觀察中,隨接觸之檳榔鹼濃度的上升,肌小纖維(myofibrils)間出現明顯的空泡狀、粒線體也受到嚴重破壞;透過RT-PCR觀察與粒線體相關的基因如sdhb、coxI、cox4i1、atp5a1、atp5f1在48及96hpf各基因的表現量,皆隨接觸之檳榔鹼濃度的上升而下降;此外,JC-1檢測結果顯示,隨接觸之檳榔鹼濃度的上升,粒線體膜電位受到影響的比例也會增加。
由以上之研究結果,吾人得知:檳榔鹼會造成胚胎的存活率下降、游泳活動能力受限、胚胎發育遲緩、骨骼肌發育受損、粒線體結構及功能受到破壞。由此觀之,雖短時間之接觸檳榔鹼,亦可能對受孕、早產及胎兒之發育造成嚴重之影響。


Arecoline, a major alkaloid in areca nuts, is involved in the pathogenesis of inflammatory oral diseases, cancers and in the developmentally toxic effect of lowering weight and retarding growth of the embryo.
Experiment I:Mammalian taste buds are the basic structural unit for detecting taste stimuli in the oral cavity, however, the effects of arecoline on the taste bud are poorly understood. We injected arecoline intraperitoneally into C57BL/6 mice twice daily for 1 - 4 weeks and aimed to revealthe taste bud morphology, life span and gustatory functional activity by immunohistochemistry (IHC) and electron microscopy.
At end of arecoline treatment, the animals were sacrificed through perfusion, and the vallate papillae were excised and processed for electron microscopy and immunohistochemistry (IHC) analysis of taste receptor proteins (T1R2, T1R3, T1R1 and T2R) and taste associated proteins (α-gustducin, PLCβ2 and SNAP25). Expression levels of c-fos were detected in the solitary nucleus and gustatory cortex. Body weight, food intake and water consumption were recorded during the treatment period every other day. After arecoline treatment, a two-bottle preference test between water and 1 % sucrose was performed for 4 weeks. For study of taste bud cells life-span, mice were also injected with BrdU (50 mg/kg i.p.) at end of arecoline treatment and then perfused at day 1 to day 14 following BrdU administration.
The results demonstrated that (1) arecoline treatment did not change the number and size of the taste buds, and the number of taste bud cells was not affected, (2) electron microscopy revealed the swollen mitochondria, dilated endoplasmic reticulum cisternae, and numerous irregular autophagosomes accumulated in type II cells, (3) IHC demonstrated a decrease in the number of taste receptor T1R2- and T1R3-expressing cells, (4) the level of c-fos expression was decreased in the solitary nucleus and gustatory cortex, (5) the body weight and food intake amount were markedly reduced, (6) the sweet preference behaviour was-reduced, (7) the number of BrdU-labeled taste bud cells was significant reduced at 1, 3, 7 and 14 days, and (8) PCR array experiments showed that the expression of cyclin B2 and E2F1, was markedly downregulated, but the expression of p53 and bax was markedly upregulated by arecoline in the circumvallate.
We conclude that the long-term arecoline injection alters the morphology of type II taste bud cells, retards the growth of mice from puberty to adulthood, affects gustatory discrimination competencies, also inhibits taste progenitor cells proliferation and shorten life span of renew taste bud cells.

Experiment II:The effects of arecoline on birth defects have been explored in many species, including chicken, mice, and zebrafish. The effects of arecoline on embryos after long-term exposure are well established, however, the effects of short-term arecoline exposure to embryos are not fully understood. Using zebrafish as an animal model, we studied the effects of short-term exposure of arecoline on zebrafish embryos to mimic the areca nut-chewing woman during early pregnancy. Arecoline, at concentrations from 0.001 to 0.04%, was administered to zebrafish embryos from 4 to 24 hpf (hours post fertilization). The morphological changes, hatching and survival rates, body length, and somitic skeletal muscle fiber structure were investigated by immunohistochemistry (IHC), confocal microscopy, and conventional electron microscopy.
With exposure of zebrafish embryos to the increasing concentrations of arecoline, we observed a significant decline in the hatching and survival rates, general growth retardation, lower locomotor activity and impairment of swimming ability. Immuno-fluorescence staining demonstrated a loose arrangement of myosin heavy chains, and ultrastructural observations revealed an altered arrangement of somitic myofibril and swelling of the mitochondria. In addition, the results from flow-cytometry, JC-1 staining to assay mitochondria activity, and RT-PCR analysis of mitochondrial functional gene expression, revealed mitochondrial dysfunctions after exposure to arecoline.
We confirmed that short-term arecoline exposure resulted in retarded embryonic development and decreased locomotor activity due to defective somitic skeletal muscle development and mitochondrial dysfunction.


誌謝....................................................i
中文摘要................................................ii
英文摘要 ................................................v
第一章 檳榔鹼對小鼠味蕾的影響..............................1
緒言....................................................2
前言....................................................2
檳榔鹼..................................................2
檳榔鹼與口腔相關研究.....................................5
味蕾...................................................6
味蕾的超微結構..........................................6
味蕾中味覺接受器和味覺功能標識蛋白.........................7
味蕾細胞的生命期限和更替週期..............................8
味覺障礙................................................9
研究目的................................................11
材料與方法..............................................12
實驗動物................................................12
藥物及抗體..............................................12
檳榔鹼處理..............................................12
5-溴脱氧尿嘧啶核苷標記實驗................................12
舌上皮組織分離..........................................13
灌流及冷凍切片..........................................13
組織染色................................................14
免疫螢光染色法..........................................14
組織免疫染色法..........................................14
ELISA評估口腔黏膜cytokine的變化..........................15
電子顯微觀察............................................16
掃描式電子顯微鏡掃描.....................................16
穿透式電子顯微..........................................16
反轉錄聚合酶連鎖反應.....................................17
行為實驗................................................17
生理紀錄 (體重、食物攝取量、飲水總量)......................17
雙瓶自由選擇飲水實驗.....................................17
味蕾型態學計量分析 .......................................17
統計分析................................................18
研究結果................................................19
檳榔鹼對輪廓狀乳突上味蕾數量及大小的觀察...................19
檳榔鹼對味蕾細胞超微結構的影響............................19
檳榔鹼對味覺接受蛋白和味覺相關蛋白免疫螢光染色觀察..........21
檳榔鹼對孤立束核和味覺皮質區核區的影響.....................22
檳榔鹼影響小鼠攝食、飲水及喜好度行為觀察...................22
榔鹼對舌上皮發炎細胞激素的影響............................23
檳榔鹼對味蕾新細胞更替速率的影響..........................23
檳榔鹼對味蕾細胞新生調控基因的影響........................24
討論...................................................25
檳榔鹼研究的動物模式.....................................25
檳榔鹼不影響味蕾數量、大小及味蕾細胞數.....................26
檳榔鹼對味蕾細胞超顯微的影響..............................27
檳榔鹼對甜味覺的影響.....................................28
檳榔鹼對味蕾細胞生命期限的影響............................29
參考文獻................................................32
圖表...................................................40
表1 本實驗所使用抗體和藥品列表............................41
表2 本實驗所使用引子序列表................................42
表3 檳榔鹼對味蕾大小、數量和所含味蕾細胞數量影響統計表.......43
圖5 味蕾型態的觀察.......................................44
圖6 小黑鼠接受檳榔鹼處理後,味蕾超微結構之觀察與分析........46
圖7 小黑鼠接受檳榔鹼處理後,以電子顯微鏡觀察檳榔鹼對第二型味蕾細胞的影響................................................48
圖8 電子顯微鏡觀察檳榔鹼對第二型味蕾細胞的影響..............50
圖9 味蕾之味覺相關蛋白免疫螢光染色切片.....................52
圖10 檳榔鹼對味覺相關蛋白的影響...........................54
圖11 c-fos在味覺相關核區中,免疫組織化學染色切片圖及變化....56
圖12 小黑鼠給予檳榔鹼處理後,對體重、攝食量 及飲水量的變化...58
圖13 雙瓶偏好行為測試....................................60
圖14 口腔黏膜細胞激素的表現...............................62
圖15 味蕾上干擾素伽瑪免疫螢光染色切片......................64
圖16 味蕾BrdU免疫螢光染色................................66
圖17 各組BrdU變化情形...................................68
圖18 RT-PCR電泳圖及統計變化圖............................70
第二章 檳榔鹼對斑馬魚胚胎體節的影響........................72
前言...................................................73
檳榔鹼造成的胚胎畸形.....................................73
斑馬魚Zebrafish (Danio rerio)..........................74
斑馬魚的骨骼肌發育 .......................................74
檳榔鹼在斑馬魚上的研究...................................75
檳榔鹼對粒線體的影響.....................................76研究目的................................................77
材料與方法..............................................78
斑馬魚胚胎之培養.........................................78
檳榔鹼 (Arecoline) 之處理...............................78
胚胎之觀察記錄及照相.....................................79
斑馬魚游泳形態紀錄及距離分析..............................79
全標本包埋免疫組織化學染色及共軛焦顯微拍照..................79
穿透式電子顯微..........................................80
反轉錄聚合酶鏈鎖反應.....................................80
分離粒線體..............................................81
粒線體膜電位............................................81
數據圖表和統計整理 .......................................81
結果...................................................83
斑馬魚胚胎經檳榔鹼培養後存活率與孵化率之影響................83
斑馬魚胚胎經檳榔鹼處理後之表現型態.........................84
斑馬魚胚胎經檳榔鹼處理後之長度與身體尾巴彎曲角度統計分析.....85
檳榔鹼處理對斑馬魚胚胎運動功能的影響 .......................86
檳榔鹼處理對斑馬魚胚胎肌纖維的影響 -- 免疫螢光染色..........87
檳榔鹼處理對斑馬魚胚胎肌纖維的影響 – 電子顯微鏡觀察結果......88
檳榔鹼處理對斑馬魚胚胎肌纖維中粒線體RNA的影響...............89
檳榔鹼處理對斑馬魚胚胎肌纖維中粒線體膜電位的影響............89
討論...................................................91
斑馬魚胚胎經檳榔鹼培養後降低存活率.........................91
檳榔鹼對斑馬魚胚胎運動功能的影響..........................91
檳榔鹼對斑馬魚胚胎肌節骨骼肌的影響.........................92
檳榔鹼對粒線體的影響.....................................93
參考文獻...............................................96
圖表..................................................100
表1 本實驗所使用抗體和藥品列表...........................101
表2 本實驗所使用引子序列表...............................102
圖2 檳榔鹼處理對於胚胎存活率和孵化率之影響................103
圖3 檳榔鹼處理之後胚胎整體型態改變情形....................105
圖4 以檳榔鹼處理之後斑馬魚整體長度、身體與尾巴角度、游泳軌跡和游泳長度之改變...........................................107
圖5 斑馬魚尾部肌節之myosin heavy chain 免疫螢光染色......109
圖6 以不同濃度檳榔鹼處理的斑馬魚胚胎,尾段肌肉組織之超微結構111
圖7 以不同濃度檳榔鹼處理的斑馬魚胚胎,尾段肌肉組織之超微結構113
圖8 RT-PCR電泳圖及統計變化圖............................115
圖9 不同檳榔鹼濃度處理下各組對粒線體膜電位的影響...........119
結論..................................................121
第三章 擬繼續之工作.....................................122
研究背景...............................................123
預期結果...............................................126
參考文獻...............................................129


partI
Alshadwi A, Bhatia I. 2012. Excision of oral submucous fibrosis and reconstruction with full thickness skin graft: a case study and review of the literature. Case Rep Dent 2012: 628-630.
Barry MA, Frank ME. 1992. Response of the gustatory system to peripheral nerve injury. Exp Neurol 115: 60-64.
Beidler LM, Smallman RL. 1965. Renewal of cells within taste buds. J Cell Biol. 27: 263-265.
Bigiani A. 2001. Mouse taste cells with glialike membrane properties. J. Neurophysiol. 85 : 1552-1560.
Bogdanov OV. 1961. The effect of arecoline on the cardiac activity of the chick of the chick embryo at various stages of its development. Bull Exp Biol Med. 50: 1153-1157.
Bolze MS, Fosmire GJ, Stryker JA, Chung CK, Flipse BG. 1982. Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships. Radiology 144: 163-169.
Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng LX, Guo W, Zuker CS, Ryba NJP. 2000. T2Rs function as bitter taste receptors. Cell 100: 703-711.
Chang MC. 2001. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22: 1527-1535.
Chang NW, Pei RJ, Tseng HC, Yeh KT, Chan HC, Lee MR, Lin C, Hsieh WT, Kao MC, Tsai MH, Lin CF. 2010. Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse model mimicking oral tumorigenesis. Chem Biol Interact 183: 231-238.
Chang YC, Lii CK, Tai KW, Chou MY. 2001. Adverse effects of arecoline and nicotine on human periodontal ligament fibroblasts in vitro. J Clin Periodontol 28: 277-282.
Chang YC, Tai KW, Lii CK, Chou LS, Chou MY. 1999. Cytopathologic effects of arecoline on human gingival fibroblasts in vitro. Clin Oral Investig 3: 25-29.
Chase LR, Melson GL, Aurbach GD. 1969. Pseudohypoparathyroidism: defective excretion of 3′,5′-AMP in response to parathyroid hormone. J Clin Invest. 48: 1832-1844.
Chatterjee A, Deb S. 1999. Genotoxic effect of arecoline given either by the peritoneal or oral route in murine bone marrow cells and the influence of N-acetylcysteine. Cancer Lett 139: 23-31.
Cheng HL, Su SJ, Huang LW, Hsieh BS, Hu YC, Hung TC, Chang KL. 2010. Arecoline induces HA22T/VGH hepatoma cells to undergo anoikis - involvement of STAT3 and RhoA activation. Mol Cancer 9: 126-130.
Chiang CP, Chang MC, Lee JJ, Chang JY, Lee PH, Hahn LJ, Jeng JH. 2004. Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch. Oral Oncol 40: 720-727.
Chou HC, Chien CL, Huang HL, Lu KS. 2001. Effects of zinc deficiency on the vallate papillae and taste buds in rats. J Formos Med Assoc. 100: 326-335.
Cohn ZJ, Kim A, Huang L, Brand J, Wang H. 2010. Lipopolysaccharide-induced inflammation attenuates taste progenitor cell proliferation and shortens the life span of taste bud cells. BMC Neurosci 11: 72-84.
Conger AD, Wells MA. 1969. Radiation and aging effect on taste structure and function. Radiat Res 37: 31-49.
Dasgupta R, Saha I, Pal S, Bhattacharyya A, Sa G, Nag TC, Das T, Maiti BR. 2006. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice. Toxicology 227: 94-104.
Delay RJ, Kinnamon JC, Roper SD. 1986. Ultrastructure of mouse vallate taste buds: II. Cell types and cell lineage. J Comp Neurol 253: 242-252.
Farbman AI. 1969. Fine structure of degenerating taste buds after denervation. J Embryol Exp Morph 22: 55-60.
Farbman AI, Hellekant G, Nelson A. 1985. Structure of taste buds in foliate papillae of the rhesus monkey, Macaca mulatta. Am J Anat. 172: 41-56.
Finger TE. 2005. Cell types and lineages in taste buds. Chem Senses 30 Suppl 1: i54-65.
Giri S, Idle JR, Chen C, Zabriskie TM, Krausz KW, Gonzalez FJ. 2006. A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse. Chem Res Toxicol 19: 818-827.
Guagliardo NA, Hill DL. 2007. Fungiform taste bud degeneration in C57BL/6J mice following chorda-lingual nerve transection. J Comp Neurol 504: 206-216.
Gupta PC, Ray CS. 2004. Epidemiology of betel quid usage. Ann Acad Med Singapore. 33: 31-36.
Hamamichi R, Asano-Miyoshi M, Emori Y. 2006. Taste bud contains both short-lived and long-lived cell populations. Neuroscience 141: 2129-2138.
Harrison TA, Smith Adams LB, Moore PD, Perna MK, Sword JD, Defoe DM. 2011. Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1. BMC Neurosci 12: 34-40.
Heck GL, Mierson S, Desimone JA. 1984. Salt taste transduction occurs through an amiloride-sensitive sodium-transport pathway. Science 223: 403-405.
Hendricks SJ, Brunjes PC, Hill DL. 2004. Taste bud cell dynamics during normal and sodium-restricted development. J Comp Neurol 472: 173-182.
Henkin RI. 1994. Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction. Drug Saf 11: 318-328.
Henkin RI, Gill JR, Bartter FC. 1963. Studies on taste thresholds in normal man and in patients with adrenal cortical insufficiency: The role of adrenal cortical steroids and of serum sodium concentration. J Clin Invest.. 42: 727-735.
Herness MS. 1992. Aldosterone increases the amiloride-sensitivity of the rat gustatory neural response to NaCl. Comp Biochem Physiol Comp Physiol. 103: 269-273.
Hevezi P, Moyer BD, Lu M, Gao N, White E, Echeverri F, Kalabat D, Soto H, Laita B, Li C, Yeh SA, Zoller M, Zlotnik A. 2009. Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes. PLoS One 4: e6395.
Huang AL, Chen X, Hoon MA, Chandrashekar J, Guo W, Trankner D, Ryba NJ, Zuker CS. 2006. The cells and logic for mammalian sour taste detection. Nature 442: 934-938.
Huang YJ, Lu KS. 2001. TUNEL staining and electron microscopy studies of apoptotic changes in the guinea pig vallate taste cells after unilateral glossopharyngeal denervation. Anat Embryol (Berl). 204: 493-501.
IARC. 1985. Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines. IARC Working Group. Lyon, 23-30 October 1984.
IARC. 2004. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC monographs on the evaluation of carcinogenic risks to humans / World Health Organization, IARC 85: 1-334.
Ichikawa H, Terayama R, Yamaai T, De Repentigny Y, Kothary R, Sugimoto T. 2007. Dystonin deficiency reduces taste buds and fungiform papillae in the anterior part of the tongue. Brain Res 1129: 142-146.
Ishimaru Y, Inada H, Kubota M, Zhuang H, Tominaga M, Matsunami H. 2006. Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci U S A. 103: 12569-12574.
Jayanthi V, Probert CS, Sher KS, Mayberry JF. 1992. Oral submucosal fibrosis--a preventable disease. Gut 33: 4-6.
Jeng JH, Chang MC, Hahn LJ. 2001. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol 37: 477-492.
Jeng JH, Ho YS, Chan CP, Wang YJ, Hahn LJ, Lei D, Hsu CC, Chang MC. 2000. Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. Carcinogenesis 21: 1365-1370.
Jeng JH, Lan WH, Hahn LJ, Hsieh CC, Kuo MY. 1996. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med. 25: 371-375.
Jeng JH, Wang YJ, Chiang BL, Lee PH, Chan CP, Ho YS, Wang TM, Lee JJ, Hahn LJ, Chang MC. 2003. Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24: 1301-1315.
Kasahara Y, Shimotahira K. 1977. [A study on the gustatory effects of tetrodotoxin in rat (author''s transl)]. Nihon Seirigaku Zasshi 39: 105-111.
King CT, Travers SP, Rowland NE, Garcea M, Spector AC. 1999. Glossopharyngeal nerve transection eliminates quinine-stimulated fos-like immunoreactivity in the nucleus of the solitary tract: implications for a functional topography of gustatory nerve input in rats. J Neurosci 19: 3107-3121.
Kinnamon JC, Henzler DM, Royer SM. 1993. HVEM ultrastructural analysis of mouse fungiform taste buds, cell types, and associated synapses. Microsc Res Tech 26: 142-156.
Kinnamon JC, Sherman TA, Roper SD. 1988. Ultrastructure of mouse vallate taste buds: III. Patterns of synaptic connectivity. J Comp Neurol 270: 1-10.
Kinnamon JC, Taylor BJ, Delay RJ, Roper SD. 1985. Ultrastructure of mouse vallate taste buds. I. Taste cells and their associated synapses. J Comp Neurol 235: 48-60.
Klionsky DJ, Emr SD. 2000. Cell biology - Autophagy as a regulated pathway of cellular degradation. Science 290: 1717-1721.
Ko YC, Chiang TA, Chang SJ, Hsieh SF. 1992. Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med. 21: 261-264.
Koyama H. 1972. Effect of 5-bromodeoxyuridine on gene expression in mammalian cells. Tanpakushitsu Kakusan Koso 17: 461-469.
Lawton DM, Furness DN, Lindemann B, Hackney CM. 2000. Localization of the glutamate-aspartate transporter, GLAST, in rat taste buds. Eur. J. Neurosc. 12: 3163-3171.
Lee PH, Chang MC, Chang WH, Wang TM, Wang YJ, Hahn LJ, Ho YS, Lin CY, Jeng JH. 2006. Prolonged exposure to arecoline arrested human KB epithelial cell growth: regulatory mechanisms of cell cycle and apoptosis. Toxicology 220: 81-89.
Lin LC, Que J, Lin LK, Lin FC. 2006. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. IJROBP 65: 745-750.
Lin W, Finger TE, Rossier BC, Kinnamon SC. 1999. Epithelial Na+ channel subunits in rat taste cells: localization and regulation by aldosterone. J Comp Neurol 405: 406-420.
Liu ST, Young GC, Lee YC, Chang YF. 2011. A preliminary report on the toxicity of arecoline on early pregnancy in mice. Food Chem Toxicol 49: 144-148.
Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M. 2009. Autophagy is required to maintain muscle mass. Cell Metab 10: 507-515.
Mattes-Kulig DA, Henkin RI. 1985. Energy and nutrient consumption of patients with dysgeusia. J Am Diet Assoc 85: 822-826.
McConnell RJ, Menendez CE, Smith FR, Henkin RI, Rivlin RS. 1975. Defects of taste and smell in patients with hypothyroidism. Am J Med 59: 354-364.
Mistretta CM, Goosens KA, Farinas I, Reichardt LF. 1999. Alterations in size, number, and morphology of gustatory papillae and taste buds in BDNF null mutant mice demonstrate neural dependence of developing taste organs. J Comp Neurol 409: 13-24.
Miura H, Kusakabe Y, Harada S. 2006. Cell lineage and differentiation in taste buds. Arch Histol Cytol 69: 209-225.
Miyazaki M, Sugawara E, Yoshimura T, Yamazaki H, Kamataki T. 2005. Mutagenic activation of betel quid-specific N-nitrosamines catalyzed by human cytochrome P450 coexpressed with NADPH-cytochrome P450 reductase in Salmonella typhimurium YG7108. Mutat Res 581: 165-171.
Murray RG. 1986. The mammalian taste bud type III cell: a critical analysis. J Ultrastruct Mol Struct Res 95: 175-188.
Murray RG, Murray A, Fujimoto S. 1969. Fine structure of gustatory cells in rabbit taste buds. J Ultrastruct Res 27: 444-461.
Nair J, Ohshima H, Friesen M, Croisy A, Bhide SV, Bartsch H. 1985. Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis 6: 295-303.
Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS. 2002. An amino-acid taste receptor. Nature 416: 199-202.
Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. 2001. Mammalian sweet taste receptors. Cell 106: 381-390.
Nery R. 1971. The metabolic interconversion of arecoline and arecoline 1-oxide in the rat. Biochem J 122: 503-508.
Noguchi T, Ikeda Y, Miyajima M, Yoshii K. 2003. Voltage-gated channels involved in taste responses and characterizing taste bud cells in mouse soft palates. Brain Res 982: 241-259.
Ohtubo Y, Yoshii K. 2011. Quantitative analysis of taste bud cell numbers in fungiform and soft palate taste buds of mice. Brain Res 1367: 13-21.
Pai MH, Ko TL, Chou HC. 2007. Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae. Acta Histochem 109: 200-207.
Panigrahi GB, Rao AR. 1982. Chromosome-breaking ability of arecoline, a major betel-nut alkaloid, in mouse bone-marrow cells in vivo. Mutat Res 103: 197-204.
Paul K, Moitra PK, Mukherjee I, Maity C, Ghosal SK. 1999. Teratogenicity of arecoline hydrobromide on developing chick embryos: a preliminary report. Bull Environ Contam Toxicol. 62: 356-362.
Perea-Martinez I, Nagai T, Chaudhari N. 2013. Functional cell types in taste buds have distinct longevities. PLoS One 8: e53399.
Pfeiffer CC, Beck RA, Goldstein L. 1967. The modification of central nervous system (cns) function by autonomic drugs. Amine shift responses differentiate between cns nicotinic and muscarinic effects. Ann Ny Acad Sci 142: 181-189.
Raghavan V, Baruah HK. 1958. Arecanut: India’s popular masticatory —history, chemistry and utilization. Econ Botan. 12: 315-345.
Ranadive KJ, Gothoskar SV, Rao AR, Tezabwalla BU, Ambaye RY. 1976. Experimental studies on betel nut and tobacco carcinogenicity. Int J Cancer 17: 469-476.
Reichart PA. 1995. Oral cancer and precancer related to betel and miang chewing in Thailand: a review. J Oral Pathol Med 24: 241-243.
Rollin H. 1978. Drug-related gustatory disorders. Ann Oto Rhinol Laryn 87: 37-42.
Roper SD. 1989. The cell biology of vertebrate taste receptors. Annu Rev Neurosci 12: 329-353.
Royer SM, Kinnamon JC. 1988. Ultrastructure of mouse foliate taste-buds - synaptic and nonsynaptic interactions between taste cells and nerve-fibers. J Comp Neurol. 270: 11-15.
Salminen A, Kaarniranta K. 2009. Regulation of the aging process by autophagy. Trends Mol Med 15: 217-224.
Sandow PL, Hejrat-Yazdi M, Heft MW. 2006. Taste loss and recovery following radiation therapy. J Dent Res 85: 608-611.
Selvan RS, Selvakumaran M, Rao AR. 1991. Influence of arecoline on immune system: II. Suppression of thymus-dependent immune responses and parameter of non-specific resistance after short-term exposure. Immunopharm Immunot 13: 281-309.
Sheng M, Greenberg ME. 1990. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4: 477-485.
Simon SA, de Araujo IE, Gutierrez R, Nicolelis MA. 2006. The neural mechanisms of gustation: a distributed processing code. Nat Rev Neurosci 7: 890-901.
Stich HF, Stich W, Lam PPS. 1981. Potentiation of genotoxicity by concurrent application of compounds found in betel quid - arecoline, eugenol, quercetin, chlorogenic acid and Mn2+. Mutat Res 90: 355-363.
Sweazey RD, Edwards CA, Kapp BM. 1994. Fine structure of taste buds located on the lamb epiglottis. Anat Rec 238: 517-527.
Takeda M. 1976. An electron microscopic study on the innervation in the taste buds of the mouse circumvallate papillae. Arch Histol Jpn 39: 257-269.
Takeda M, Hoshino T. 1975. Fine structure of taste buds in the rat. Arch Histol Jpn. 37: 395-413.
Takeda M, Suzuki Y, Obara N, Nagai Y. 1996. Apoptosis in mouse taste buds after denervation. Cell Tissue Res 286: 55-62.
Takeda M, Suzuki Y, Obara N, Nagai Y. 2000. Induction of apoptosis by colchicine in taste bud and epithelial cells of the mouse circumvallate papillae. Cell Tissue Res 302: 391-395.
Temussi PA. 2009. Sweet, bitter and umami receptors: a complex relationship. Trends Biochem Sci 34: 296-302.
Tordoff MG. 2007. Taste solution preferences of C57BL/6J and 129X1/SvJ mice: influence of age, sex, and diet. Chem Senses 32: 655-671.
Tordoff MG, Bachmanov AA. 2003. Mouse taste preference tests: why only two bottles? Chem Senses 28: 315-324.
Trivedy CR, Craig G, Warnakulasuriya S. 2002. The oral health consequences of chewing areca nut. Addict Biol 7: 115-125.
Wall PL, McCluskey LP. 2008. Rapid changes in gustatory function induced by contralateral nerve injury and sodium depletion. Chem Senses 33: 125-135.
Wang H, Zhou M, Brand J, Huang L. 2009. Inflammation and taste disorders: mechanisms in taste buds. Ann NY Acad Sci 1170: 596-603.
Wenzel PL, Chong JL, Saenz-Robles MT, Ferrey A, Hagan JP, Gomez YM, Rajmohan R, Sharma N, Chen HZ, Pipas JM, Robinson ML, Leone G. 2011. Cell proliferation in the absence of E2F1-3. Dev Biol 351: 35-45.
Winstock A. 2002. Areca nut-abuse liability, dependence and public health. Addict Biol 7: 133-138.
Witte KK, Clark AL. 2002. Nutritional abnormalities contributing to cachexia in chronic illness. Int J Cardiol 85: 23-31.
Wong GT, Gannon KS, Margolskee RF. 1996. Transduction of bitter and sweet taste by gustducin. Nature 381: 796-800.
Wu IC, Chen PH, Wang CJ, Wu DC, Tsai SM, Chao MR, Chen BH, Lee HH, Lee CH, Ko YC. 2010. Quantification of blood betel quid alkaloids and urinary 8-hydroxydeoxyguanosine in humans and their association with betel chewing habits. J Anal Toxicol. 34: 325-331.
Yamamoto T, Sako N, Sakai N, Iwafune A. 1997. Gustatory and visceral inputs to the amygdala of the rat: conditioned taste aversion and induction of c-fos-like immunoreactivity. Neurosci Lett 226: 127-130.
Yamamoto T, Sawa K. 2000. Comparison of c-fos-like immunoreactivity in the brainstem following intraoral and intragastric infusions of chemical solutions in rats. Brain Res 866: 144-151.
Yamamoto T, Shimura T, Sakai N, Ozaki N. 1994. Representation of hedonics and quality of taste stimuli in the parabrachial nucleus of the rat. Physiol Behav 56: 1197-1202.
Yamasaki L, Bronson R, Williams BO, Dyson NJ, Harlow E, Jacks T. 1998. Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice. Nat Genet 18: 360-364.
Yang R, Stoick CL, Kinnamon JC. 2004. Synaptobrevin-2-like immunoreactivity is associated with vesicles at synapses in rat circumvallate taste buds. J Comp Neurol 471: 59-71.
Yang YM, Bauer C, Strasser G, Wollman R, Julien JP, Fuchs E. 1999. Integrators of the cytoskeleton that stabilize microtubules. Cell 98: 229-238.
Yasumatsu K, Kusuhara Y, Shigemura N, Ninomiya Y. 2007. Recovery of two independent sweet taste systems during regeneration of the mouse chorda tympani nerve after nerve crush. Eur J Neurosci 26: 1521-1519.
Yoshie S, Wakasugi C, Teraki Y, Fujita T. 1990. Fine structure of the taste bud in guinea pigs. I. Cell characterization and innervation patterns. Arch Histol Cytol 53: 103-119.
Zeng Q, Kwan A, Oakley B. 2000. Gustatory innervation and bax-dependent caspase-2: participants in the life and death pathways of mouse taste receptor cells. J Comp Neurol 424: 640-650.
Zeng Q, Oakley B. 1999. p53 and Bax: putative death factors in taste cell turnover. J Comp Neurol 413: 168-180.
Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, Zuker CS. 2003. The receptors for mammalian sweet and umami taste. Cell 115: 255-266.
Zhou ZS, Li M, Gao F, Peng JY, Xiao HB, Dai LX, Lin SR, Zhang R, Jin LY. 2013. Arecoline suppresses HaCaT cell proliferation through cell cycle regulatory molecules. Oncol Rep 29: 2438-2444.


part II
Akhtar S, Sheikh AA, Qureshi HU. 2012. Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of oesophageal squamous-cell carcinoma in South Asians: a multicentre case-control study. Eur J Cancer 48: 655-661.
Anichtchik O, Diekmann H, Fleming A, Roach A, Goldsmith P, Rubinsztein DC. 2008. Loss of PINK1 function affects development and results in neurodegeneration in zebrafish. J Neurosci 28: 8199-8207.
Anras MLB, Lagardere JP. 2004. Measuring cultured fish swimming behaviour: first results on rainbow trout using acoustic telemetry in tanks. Aquaculture 240: 175-186.
Blagden CS, Currie PD, Ingham PW, Hughes SM. 1997. Notochord induction of zebrafish slow muscle mediated by Sonic hedgehog. Genes & Development 11: 2163-2175.
Boucher BJ, Mannan N. 2002. Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Addict Biol 7: 49-55.
Chang BE, Liao MH, Kuo MY, Chen CH. 2004. Developmental toxicity of arecoline, the major alkaloid in betel nuts, in zebrafish embryos. Birth Defects Res A Clin Mol Teratol 70: 28-36.
Chang MC, Ho YS, Lee PH, Chan CP, Lee JJ, Hahn LJ, Wang YJ, Jeng JH. 2001. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22: 1527-1535.
Chang YF, Liu TY, Liu ST, Tseng CN. 2012. Arecoline inhibits myogenic differentiation of C2C12 myoblasts by reducing STAT3 phosphorylation. Food Chem Toxicol 50: 3433-3439.
Chen TH, Chiu YH, Boucher BJ. 2006. Transgenerational effects of betel-quid chewing on the development of the metabolic syndrome in the Keelung Community-based Integrated Screening Program. Am J Clin Nutr 83: 688-692.
Chen YH, Huang YH, Wen CC, Wang YH, Chen WL, Chen LC, Tsay HJ. 2008. Movement disorder and neuromuscular change in zebrafish embryos after exposure to caffeine. Neurotoxicol Teratol 30: 440-447.
Chinnery PF, Turnbull DM. 1999. Mitochondrial DNA and disease. Lancet 354 Suppl 1: SI17-21.
Currie PD, Ingham PW. 1998. The generation and interpretation of positional information within the vertebrate myotome. Mech Develop 73: 3-21.
de Costa C, Griew AR. 1982. Effects of betel chewing on pregnancy outcome. Aust N Z J Obstet Gynaecol 22: 22-24.
Eaton RC, Lee RK, Foreman MB. 2001. The Mauthner cell and other identified neurons of the brainstem escape network of fish. Prog Neurobiol 63: 467-485.
Fero K, Yokogawa T, Burgess H. 2011. The behavioral repertoire of larval zebrafish. In: Kalueff AV, Cachat JM, editors, Zebrafish models in neurobehavioral research. Humana Press. New York, 86: 249-291.
Hassoun E, Kariya C, Williams F. 2005. Dichloroacetate‐induced developmental toxicity and production of reactive oxygen species in zebrafish embryos. J Biochem Mol Toxicol. 19: 52-58.
Hill AJ, Teraoka H, Heideman W, Peterson RE. 2005. Zebrafish as a model vertebrate for investigating chemical toxicity. Toxicol Sci 86: 6-19.
Huang H, Huang C, Wang L, Ye X, Bai C, Simonich MT, Tanguay RL, Dong Q. 2010. Toxicity, uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid (PFOS). Aquat Toxicol 98: 139-147.
Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. 1995. Stages of embryonic development of the zebrafish. Dev Dyn 203: 253-310.
Kohler SA, Henderson BR, Kuhn LC. 1995. Succinate dehydrogenase b mrna of drosophila melanogaster has a functional iron-responsive element in its 5''-untranslated region. J Biol Chem. 270: 30781-30786.
Lerebours A, Adam-Guillermin C, Brethes D, Frelon S, Floriani M, Camilleri V, Garnier-Laplace J, Bourdineaud JP. 2010. Mitochondrial energetic metabolism perturbations in skeletal muscles and brain of zebrafish (Danio rerio) exposed to low concentrations of waterborne uranium. Aquat Toxicol 100: 66-74.
Lewis KE, Currie PD, Roy S, Schauerte H, Haffter P, Ingham PW. 1999. Control of muscle cell-type specification in the zebrafish embryo by Hedgehog signalling. Dev Biol 216: 469-480.
Lund BO, Miller DM, Woods JS. 1993. Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria. Biochem Pharmacol 45: 2017-2024.
Makita R, Mizuno T, Koshida S, Kuroiwa A, Takeda H. 1998. Zebrafish wnt11: pattern and regulation of the expression by the yolk cell and no tail activity. Mech Develop. 71: 165-176.
McClelland GB, Craig PM, Dhekney K, Dipardo S. 2006. Temperature- and exercise-induced gene expression and metabolic enzyme changes in skeletal muscle of adult zebrafish (Danio rerio). J Physiol 577: 739-751.
McFarland R, Taylor RW, Turnbull DM. 2002. The neurology of mitochondrial DNA disease. The Lancet. Neurol 1: 343-351.
McGonnell IM, Fowkes RC. 2006. Fishing for gene function--endocrine modelling in the zebrafish. Eur J Endocrinol 189: 425-439.
Montecucco C, Gutierrez JM, Lomonte B. 2008. Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action. CMLS 65: 2897-2912.
Muller UK, van Leeuwen JL. 2004. Swimming of larval zebrafish: ontogeny of body waves and implications for locomotory development. J. Exp. Bot. 207: 853-868.
Naganawa Y, Hirata H. 2011. Developmental transition of touch response from slow muscle-mediated coilings to fast muscle-mediated burst swimming in zebrafish. Dev Biol 355: 194-204.
Nery R. 1971. The metabolic interconversion of arecoline and arecoline 1-oxide in the rat. Biochem J 122: 503-508.
Nimkerdphol K, Nakagawa M. 2008. Effect of sodium hypochlorite on zebrafish swimming behavior estimated by fractal dimension analysis. J Biosci Bioeng 105: 486-492.
Paul K, Moitra PK, Mukherjee I, Maity C, Ghosal SK. 1999. Teratogenicity of arecoline hydrobromide on developing chick embryos: a preliminary report. Bull Environ Contam Toxicol. 62: 356-362.
Pichini S, Puig C, Zuccaro P, Marchei E, Pellegrini M, Murillo J, Vall O, Pacifici R, Garcia-Algar O. 2005. Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the "Meconium Project". Forensic Sci Int 153: 59-65.
Pietri T, Manalo E, Ryan J, Saint-Amant L, Washbourne P. 2009. Glutamate drives the touch response through a rostral loop in the spinal cord of zebrafish embryos. Dev Neurobiol 69: 780-795.
Saint-Amant L, Drapeau P. 1998. Time course of the development of motor behaviors in the zebrafish embryo. J Neurobiol 37: 622-632.
Senn M, Baiwog F, Winmai J, Mueller I, Rogerson S, Senn N. 2009. Betel nut chewing during pregnancy, Madang province, Papua New Guinea. Drug Alcohol Depend 105: 126-131.
Seyer P, Grandemange S, Busson M, Carazo A, Gamaléri F, Pessemesse L, Casas F, Cabello G, Wrutniak‐C. 2006. Mitochondrial activity regulates myoblast differentiation by control of c‐Myc expression. J Cell Physiol. 207: 75-86.
Seyer P, Grandemange S, Rochard P, Busson M, Pessemesse L, Casas F, Cabello G, Wrutniak-Cabello C. 2011. P43-dependent mitochondrial activity regulates myoblast differentiation and slow myosin isoform expression by control of c alcineurin expression. Exp Cell Res 317: 2059-2071.
Sinha A, Rao AR. 1985. Embryotoxicity of betel nuts in mice. Toxicology 37: 315-326.
Solaini G, Sgarbi G, Lenaz G, Baracca A. 2007. Evaluating mitochondrial membrane potential in cells. Biosci Rep 27: 11-21.
Spence R, Gerlach G, Lawrence C, Smith C. 2008. The behaviour and ecology of the zebrafish, Danio rerio. Biol Rev Camb Philos Soc. 83: 13-34.
Stainier DYR, Fishman MC. 1994. The zebrafish as a model system to study cardiovascular development. Trends Cardiovas Med 4: 207-212.
Stickney HL, Barresi MJF, Devoto SH. 2000b. Somite development in zebrafish. Dev Dyn 219: 287-303.
Sylvain NJ, Brewster DL, Ali DW. 2010. Zebrafish embryos exposed to alcohol undergo abnormal development of motor neurons and muscle fibers. Neurotoxicol Teratol 32: 472-480.
Thomas JK, Janz DM. 2011. Dietary selenomethionine exposure in adult zebrafish alters swimming performance, energetics and the physiological stress response. Aquat Toxicol 102: 79-86.
Tiedeken JA, Ramsdell JS, Ramsdell AF. 2005. Developmental toxicity of domoic acid in zebrafish (Danio rerio). Neurotoxicol Teratol 27: 711-717.
Waterman RE. 1969. Development of the lateral musculature in the teleost, Brachydanio rerio: a fine structural study. Am J Anat. 125: 457-493.
Yang CF, Shen HM, Ong CN. 2000. Intracellular thiol depletion causes mitochondrial permeability transition in ebselen-induced apoptosis. Arch Biochem Biophys 380: 319-330.
Yang MS, Lee CH, Chang SJ, Chung TC, Tsai EM, Ko AM, Ko YC. 2008. The effect of maternal betel quid exposure during pregnancy on adverse birth outcomes among aborigines in Taiwan. Drug Alcohol Depend 95: 134-139.
Yang MS, Su IH, Wen JK, Ko YC. 1996. Prevalence and related risk factors of betel quid chewing by adolescent students in southern Taiwan. J Oral Pathol Med. 25: 69-71.
Zhang YZ, Ouyang YC, Hou Y, Schatten H, Chen DY, Sun QY. 2008. Mitochondrial behavior during oogenesis in zebrafish: a confocal microscopy analysis. Dev Growth Differ 50: 189-201.


part III
Dudov KP, Perry RP. 1984. The gene family encoding the mouse ribosomal protein- contains a uniquely expressed intron-containing gene and an unmutated processed gene. Cell 37: 457-468.
Dyer J. 2005. Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem Soc Trans. 33: 302-305.
Feng X-H, Liu X-M, Zhou L-H, Wang J, Liu G-D. 2008. Expression of glucagon-like peptide-1 in the taste buds of rat circumvallate papilla. Acta Histochem. 110: 151-154.
Grube D, Forssmann WG. 1979. Morphology and function of the entero-endocrine
cells. Horm Metab Res. 11: 589-606.
Gunawardene AR, Corfe BM, Staton CA. 2011. Classification and functions of
enteroendocrine cells of the lower gastrointestinal tract. Int J Clin Exp Pathol. 92:
219-231.
Höfer D, Drenckhahn D. 1998. Identification of the taste cell G-protein, α-gustducin,
in brush cells of the rat pancreatic duct system. Histochemistry 110: 303-309.
Hass N, Schwarzenbacher K, Breer H. 2007. A cluster of gustducin-expressing cells in the mouse stomach associated with two distinct populations of enteroendocrine cells. Histochemistry 128: 457-471.
Jang H-J, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim B-J, Zhou J, Kim HH,Xu X, Chan SL, Juhaszova M, Bernier M, Mosinger B, Margolskee RF, Egan JM. 2007. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like
peptide-1. Proc. Natl. Acad. Sci. USA 104: 15069-15074.
Kiliaan AJ, Saunders PR, Bijlsma PB, Berin MC, Taminiau JA, Groot JA, Perdue MH. 1998. Stress stimulates transepithelial macromolecular uptake in rat jejunum. Am J Physiol Gastrol 275: G1037-G1044.
Ledouarin NM. 1986. Cell-line segregation during peripheral nervous system
ontogeny. Science 231: 1515-1522.
Martin C, Passilly-Degrace P, Chevrot M, Ancel D, Sparks SM, Drucker DJ, Besnard P. 2012. Lipid-mediated release of GLP-1 by mouse taste buds from circumvallate
papillae: Putative involvement of GPR120 and impact on taste sensitivity. J Lipid Res. 53: 2256-2265.
Nichols DB, Cheng H, Leblond CP. 1974. Variability of the shape and argentaffinity
of the granules in the enteroendcrine cells of the mouse duodenum. J Histochem Cytochem 22: 929-944.
Rombout J, Taverne JJ. 1982. An immunocytochemical and electron-microscopical study of endocrine cells in the gut and pancreas of a stomachless teleost fish, Barbus Conchonius (Cyprinidae). Cell Tissue Res 227: 577-593.
Sainz E, Korley JN, Battey JF, Sullivan SL. 2001. Identification of a novel member of the T1R family of putative taste receptors. J Neurochem. 77: 896-903.
Seta Y, Kataoka S, Toyono T, Toyoshima K. 2006. Expression of galanin and the
galanin receptor in rat taste buds. Arch Histol Cytol 69: 273-280.
Shin Y-K, Martin B, Kim W, White CM, Ji S, Sun Y, Smith RG, Sévigny J, Tschöp MH, Maudsley S, Egan JM. 2010. Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl) and sour (citric acid) tastants. PLoS ONE 5: e12729.
Sternini C. 2008. Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Curr Opin Endocrinol 15: 73-80.
Sundler F, Håkanson R, Lorén I, Lundquist I. 1980. Amine storage and function in peptide hormone-producing cells. Invest Cell Pathol 3: 87-103.
Wade PR, Westfall J. 1985. Ultrastructure of enterochromaffin cells and associated neural and vascular elements in the mouse duodenum. Cell Tissue Res 241: 557-563.
Wu SV, Chen MC, Rozengurt E. 2005. Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat. Physiol Genom 22: 139-149.
Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E. 2002. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 Cells. Proc. Ny. Acad. Sci. USA 99: 2392-2397.
Yoshida R, Ninomiya Y. New insights into the signal transmission from taste cells to gustatory nerve fibers. Int Rev Cell Mol Biol. 2010;279:101-34.
Yoshie S. 1996. Possibility of efferent innervation the rat circumvallate taste bud. Arch Histol Cytol. 59: 479-482.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
無相關點閱論文