跳到主要內容

臺灣博碩士論文加值系統

(2600:1f28:365:80b0:879a:e16d:38fe:36d8) 您好!臺灣時間:2024/12/13 07:45
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

: 
twitterline
研究生:陳郁雯
研究生(外文):Yu-WenChen
論文名稱:乙醯半胱胺酸改善杏仁核相關的自閉症行為於丙戊酸誘導的自閉症大鼠模式的機制探討
論文名稱(外文):Rescue of Amygdala-associated Autism-like Phenotypes by N-acetylcysteine in a Rat Model of Valproate-induced Autism
指導教授:簡伯武簡伯武引用關係
指導教授(外文):Po-Wu Gean
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:82
中文關鍵詞:杏仁核自閉症丙戊酸乙醯半胱胺酸
外文關鍵詞:Amygdalaautistic spectrum disordersvalproateN-acetylcysteineNAC
相關次數:
  • 被引用被引用:0
  • 點閱點閱:767
  • 評分評分:
  • 下載下載:95
  • 收藏至我的研究室書目清單書目收藏:0
背景:利用丙戊酸誘導的自閉症大鼠模式已被指出與視丘杏仁核迴路谷氨酸神經傳導過度活化有關。神經膠細胞上的胱胺酸(cysteine)/谷胺酸(glutamate)轉運蛋白將細胞外胱胺酸轉入而使谷胺酸轉出細胞外,以維持細胞外谷胺酸濃度。乙醯半胱胺酸(N-acetylcysteine ,NAC)為胱胺酸的前驅物,可藉由分解後產生的胱胺酸活化胱胺酸/谷胺酸轉運蛋白,恢復細胞外谷胺酸的濃度。因此本實驗目的,探討全身性給予乙醯半胱胺酸對於自閉症行為以及視丘杏仁核迴路突觸特性是否改變,以及代謝型谷胺酸受體第2/3型(metabotropic glutamate receptors 2/3, mGluR2/3)是否參與其中。
方法:利用丙戊酸誘發自閉症大鼠模式中,於懷孕母鼠在懷孕的12.5天時腹腔注射一劑500mg/kg丙戊酸。在出生第21天,給予公鼠子代系列的行為測試,包括社交行為測試(social interaction, SI)、開放空間行為測試(open field, OF)、高架十字迷宮測試(elevated plus maze, EPM)。行為測試結束後,腹腔注射給予乙醯半胱胺酸150mg/kg或是生理食鹽水,每天一次,為期七天。注射七天後,給予大鼠相同的行為測試。二十四小時後,犧牲大鼠,進行電生理紀錄或是西方點墨法。腹腔注射給予乙醯半胱胺酸前三十分鐘,於杏仁核局部給予代謝型谷胺酸受體第2/3型拮抗劑LY341495(每邊2ug/0.5ul),為期四天。並於局部注射LY341495一小時之後給予相同的行為測試。
結果:慢性給予丙戊酸子代乙醯半胱胺酸之後,恢復社交時間和次數以及達到緩解焦慮行為的效果。於杏仁核腦片中,丙戊酸子代有較高的mEPSCs頻率和較低的PPF比值,給予NAC之治療後得以恢復。在杏仁核局部給予mGluR2/3拮抗劑,阻斷NAC於社交行為與焦慮行為的效果。最後,丙戊酸子代於杏仁核中抑制谷胺酸神經傳導的蛋白mGluR2/3表現量改變。
結論:給予乙醯半胱胺酸治療之後,經由mGluR2/3改善丙戊酸子代的社交障礙、過度焦慮和增強的突觸前興奮性神經傳導。本實驗結果率先發現
mGluR2/3受體可做為治療丙戊酸子代自閉症症狀的新標的。

Background: Autism-like phenotypes in the male VPA-exposed offspring has been linked to high glutamatergic neurotransmission in the thalamic-amygdala pathway. Glial cystine/glutamate exchange (system Xc-), which exchanges extracellular cystine for intracellular glutamate, plays a significant role in the maintenance of extracellular glutamate. N-acetylcysteine (NAC) is a cystine prodrug that restores extracellular glutamate by stimulating cysteine system Xc-. Here, we examine the effects of systemic NAC on autism-like phenotypes and neurotransmission in thalamic–amygdala synapses, as well as the involvement of the metabotropic glutamate receptors 2/3 (mGluR2/3).
Methods: In valproate-induced model of autism, the valproate-treated rats received a single intraperitonal injection of 500 mg/kg NaVPA on E12.5. On postnatal day 21, male offspring were tested using serial behavioral tasks, including the social interaction (SI), open field (OF) and elevated plus maze (EPM) tasks. After behavioral tasks, NAC (150 mg/kg, i.p.) or saline was administered once per day for 7 days. After the 7 days injection, the rats were given the same behavioral tests. Twenty-four hours later, the rats were sacrificed for electrophysiological recordings. Intra-amygdala infusion of mGluR2/3 antagonist LY341495 (2ug/0.5ul per side) once per day for 4 days 30min before NAC. One hour after LY341495 injection, the rats were given the same behavioral tests.
Results: Chronic administration of NAC restored the duration and times of social interaction and ameliorated anxiety-like behaviors in VPA-exposed offspring. In amygdala slices, NAC treatment normalized increased frequency of mEPSCs and decreased PPF induced by VPA exposure. The effects of NAC on social interaction and anxiety in VPA-exposed offspring were blocked after intra-amygdala infusion of mGluR2/3 antagonist. Finally, protein levels from rats tissue obtained from VPA-exposured offspring revealed significant changes in the level of mGluR2/3, the active subunit for suppressing glutamatergic neurotransmission, in the amygdala.
Conclusions: The disruption of social interaction, increased anxiety and enhanced presynaptic excitatory transmission in VPA-exposed offspring could be rescued by NAC which depends on the activation of mGluR2/3. These data advance mGluR2/3 receptors as novel targets capable of reversing the autism-like phenotypes in the male VPA-exposed offspring.

第一章 緒論.......14
第一節 自閉症.......15
1.自閉症的簡介.......15
2.自閉症的疾病特徵.......15
3.自閉症的成因.......17
4.自閉症的大腦.......17
5.自閉症的藥物治療.......18
6.類似自閉症行為的動物模式.......18
第二節 丙戊酸與自閉症.......19
1.丙戊酸.......19
2.丙戊酸與自閉症的關係.......20
第三節 中樞杏仁核與自閉症.......20
1.中樞杏仁核.......20
2.中樞杏仁核與自閉症的關係.......21
第四節 乙醯半胱胺酸.......22
1.乙醯半胱胺酸.......22
2.乙醯半胱胺酸與自閉症的關係.......22
第五節 研究目的.......23
第二章 實驗目的.......29
第三章 實驗材料與方法.......31
第一節 實驗動物.......32
第二節 藥品來源.......32
第三節 實驗方法.......32
1.類似自閉症的大鼠行為模式建立....... 32
2.腦切片之製作.......33
3.全細胞膜片箝制電生理紀錄法.......34
4.腦立體定位手術.......34
5.藥物投予....... 35
6.西方點墨法.......35
7.統計方析....... 39
第四章 實驗結果.......40
第一節 3週大的丙戊酸子代具有類似自閉症行為.......41
第二節 NAC可改善丙戊酸子代社交障礙與杏仁核腦區相關行為.......42
第三節 NAC調控丙戊酸子代的杏仁核的突觸活性.......44
第四節 NAC藉由mGluR2/3受體改善丙戊酸子代社交障礙與杏仁核腦區相關行為
....... 45
第五節 丙戊酸子代杏仁核腦區mGluR2/3受體表現量降低,但cystine/glutamate轉運蛋白表現量並無改變....... 47
第五章 結論.......48
第六章 討論.......51
第一節 給予NAC於丙戊酸誘導的自閉症模式行為影響.......52
第二節 改善E/I失衡可改善自閉症.......53
第三節 mGluR2/3受體可做為治療自閉症的標靶.......54
第四節 NAC可做為開發治療自閉症的藥物的方向.......55
參考文獻.......56
圖表索引.......69

Abrahams, B.S., and Geschwind, D.H. (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nature reviews Genetics 9, 341-355.

Aldred, S., Moore, K.M., Fitzgerald, M., and Waring, R.H. (2003). Plasma amino acid levels in children with autism and their families. Journal of autism and developmental disorders 33, 93-97.

Amaral, D.G., Schumann, C.M., and Nordahl, C.W. (2008). Neuroanatomy of autism. Trends in neurosciences 31, 137-145.

American Psychiatric Association., and American Psychiatric Association. Task Force on DSM-IV. (2000). Diagnostic and statistical manual of mental disorders : DSM-IV-TR, 4th edn (Washington, DC: American Psychiatric Association).

Applegate, C.D., Frysinger, R.C., Kapp, B.S., and Gallagher, M. (1982). Multiple unit activity recorded from amygdala central nucleus during Pavlovian heart rate conditioning in rabbit. Brain Res 238, 457-462.

Aronson, M., Hagberg, B., and Gillberg, C. (1997). Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study. Developmental medicine and child neurology 39, 583-587.

Autism, Developmental Disabilities Monitoring Network Surveillance Year Principal, I., Centers for Disease, C., and Prevention (2012). Prevalence of autism spectrum disorders--Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. Morbidity and mortality weekly report Surveillance summaries 61, 1-19.

Baker, D.A., Madayag, A., Kristiansen, L.V., Meador-Woodruff, J.H., Haroutunian, V., and Raju, I. (2008). Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine. Neuropsychopharmacology 33, 1760-1772.

Baker, D.A., Xi, Z.X., Shen, H., Swanson, C.J., and Kalivas, P.W. (2002). The origin and neuronal function of in vivo nonsynaptic glutamate. The Journal of neuroscience 22, 9134-9141.

Baron-Cohen, S., Ring, H.A., Bullmore, E.T., Wheelwright, S., Ashwin, C., and Williams, S.C. (2000). The amygdala theory of autism. Neurosci Biobehav Rev 24, 355-364.

Baron-Cohen, S., Ring, H.A., Wheelwright, S., Bullmore, E.T., Brammer, M.J., Simmons, A., and Williams, S.C. (1999). Social intelligence in the normal and autistic brain: an fMRI study. Eur J Neurosci 11, 1891-1898.

Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., Judd, F., Katz, F., Katz, P., et al. (2008a). N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biological psychiatry 64, 361-368.

Berk, M., Copolov, D.L., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., and Bush, A.I. (2008b). N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial. Biological psychiatry 64, 468-475.

Bielsky, I.F., Hu, S.B., Szegda, K.L., Westphal, H., and Young, L.J. (2004). Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29, 483-493.

Bobee, S., Mariette, E., Tremblay-Leveau, H., and Caston, J. (2000). Effects of early midline cerebellar lesion on cognitive and emotional functions in the rat. Behavioural brain research 112, 107-117.

Bromley, R.L., Mawer, G., Clayton-Smith, J., and Baker, G.A. (2008). Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 71, 1923-1924.

Brothers, L., Ring, B., and Kling, A. (1990). Response of neurons in the macaque amygdala to complex social stimuli. Behav Brain Res 41, 199-213.

Buxbaum, J.D. (2009). Multiple rare variants in the etiology of autism spectrum disorders. Dialogues in clinical neuroscience 11, 35-43.

Cheng, L.L., Wang, S.J., and Gean, P.W. (1998). Serotonin depresses excitatory synaptic transmission and depolarization-evoked Ca2+ influx in rat basolateral amygdala via 5-HT1A receptors. Eur J Neurosci 10, 2163-2172.

Choleris, E., Gustafsson, J.A., Korach, K.S., Muglia, L.J., Pfaff, D.W., and Ogawa, S. (2003). An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice. Proceedings of the National Academy of Sciences of the United States of America 100, 6192-6197.

Christensen, J., Gronborg, T.K., Sorensen, M.J., Schendel, D., Parner, E.T., Pedersen, L.H., and Vestergaard, M. (2013). Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA : the journal of the American Medical Association 309, 1696-1703.

Cook, E.H., Jr. (2001). Genetics of autism. Child Adolesc Psychiatr Clin N Am 10, 333-350.

Corbett, B.A., Carmean, V., Ravizza, S., Wendelken, C., Henry, M.L., Carter, C., and Rivera, S.M. (2009). A functional and structural study of emotion and face processing in children with autism. Psychiatry research 173, 196-205.

Dalton, K.M., Nacewicz, B.M., Johnstone, T., Schaefer, H.S., Gernsbacher, M.A., Goldsmith, H.H., Alexander, A.L., and Davidson, R.J. (2005a). Gaze fixation and the neural circuitry of face processing in autism. Nature neuroscience 8, 519-526.

Dalton, K.M., Nacewicz, B.M., Johnstone, T., Schaefer, H.S., Gernsbacher, M.A., Goldsmith, H.H., Alexander, A.L., and Davidson, R.J. (2005b). Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci 8, 519-526.

Diergaarde, L., Gerrits, M.A., Brouwers, J.P., and van Ree, J.M. (2005). Early amygdala damage disrupts performance on medial prefrontal cortex-related tasks but spares spatial learning and memory in the rat. Neuroscience 130, 581-590.

DiLiberti, J.H., Farndon, P.A., Dennis, N.R., and Curry, C.J. (1984). The fetal valproate syndrome. American journal of medical genetics 19, 473-481.

Duncan, S. (2007). Teratogenesis of sodium valproate. Curr Opin Neurol 20, 175-180.

Dutta, S., Das, S., Guhathakurta, S., Sen, B., Sinha, S., Chatterjee, A., Ghosh, S., Ahmed, S., Ghosh, S., and Usha, R. (2007). Glutamate receptor 6 gene (GluR6 or GRIK2) polymorphisms in the Indian population: a genetic association study on autism spectrum disorder. Cellular and molecular neurobiology 27, 1035-1047.

Ebert, D.H., and Greenberg, M.E. (2013). Activity-dependent neuronal signalling and autism spectrum disorder. Nature 493, 327-337.

Faiella, A., Wernig, M., Consalez, G.G., Hostick, U., Hofmann, C., Hustert, E., Boncinelli, E., Balling, R., and Nadeau, J.H. (2000). A mouse model for valproate teratogenicity: parental effects, homeotic transformations, and altered HOX expression. Hum Mol Genet 9, 227-236.

Farr, S.A., Poon, H.F., Dogrukol-Ak, D., Drake, J., Banks, W.A., Eyerman, E., Butterfield, D.A., and Morley, J.E. (2003). The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. Journal of neurochemistry 84, 1173-1183.

Fatemi, S.H., Halt, A.R., Stary, J.M., Kanodia, R., Schulz, S.C., and Realmuto, G.R. (2002). Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biological psychiatry 52, 805-810.

Ferguson, J.N., Young, L.J., Hearn, E.F., Matzuk, M.M., Insel, T.R., and Winslow, J.T. (2000). Social amnesia in mice lacking the oxytocin gene. Nature genetics 25, 284-288.

Flagstad, P., Mork, A., Glenthoj, B.Y., van Beek, J., Michael-Titus, A.T., and Didriksen, M. (2004). Disruption of neurogenesis on gestational day 17 in the rat causes behavioral changes relevant to positive and negative schizophrenia symptoms and alters amphetamine-induced dopamine release in nucleus accumbens. Neuropsychopharmacology 29, 2052-2064.

Fombonne, E. (2005). Epidemiology of autistic disorder and other pervasive developmental disorders. J Clin Psychiatry 66 Suppl 10, 3-8.

Fombonne, E. (2009). Epidemiology of pervasive developmental disorders. Pediatr Res 65, 591-598.

Geschwind, D.H. (2009). Advances in autism. Annual review of medicine 60, 367-380.

Groen, W., Teluij, M., Buitelaar, J., and Tendolkar, I. (2010). Amygdala and hippocampus enlargement during adolescence in autism. J Am Acad Child Adolesc Psychiatry 49, 552-560.

Haddad, P.M., Das, A., Ashfaq, M., and Wieck, A. (2009). A review of valproate in psychiatric practice. Expert Opin Drug Metab Toxicol 5, 539-551.

Hadjikhani, N., Joseph, R.M., Snyder, J., and Tager-Flusberg, H. (2007). Abnormal activation of the social brain during face perception in autism. Hum Brain Mapp 28, 441-449.

Hardan, A.Y., Fung, L.K., Libove, R.A., Obukhanych, T.V., Nair, S., Herzenberg, L.A., Frazier, T.W., and Tirouvanziam, R. (2012). A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biological psychiatry 71, 956-961.

Harris, S.R., MacKay, L.L., and Osborn, J.A. (1995). Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports. Alcoholism, clinical and experimental research 19, 660-665.

Hazlett, H.C., Poe, M.D., Gerig, G., Styner, M., Chappell, C., Smith, R.G., Vachet, C., and Piven, J. (2011). Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years. Arch Gen Psychiatry 68, 467-476.

Henry, T.R. (2003). The history of valproate in clinical neuroscience. Psychopharmacol Bull 37 Suppl 2, 5-16.

Hess, G., Kuhnt, U., and Voronin, L.L. (1987). Quantal analysis of paired-pulse facilitation in guinea pig hippocampal slices. Neurosci Lett 77, 187-192.

Hollander, E., Phillips, A.T., and Yeh, C.C. (2003). Targeted treatments for symptom domains in child and adolescent autism. Lancet 362, 732-734.

Hsia, A.Y., Malenka, R.C., and Nicoll, R.A. (1998). Development of excitatory circuitry in the hippocampus. J Neurophysiol 79, 2013-2024.

Hultman, C.M., Sparen, P., and Cnattingius, S. (2002). Perinatal risk factors for infantile autism. Epidemiology 13, 417-423.

Jamain, S., Betancur, C., Quach, H., Philippe, A., Fellous, M., Giros, B., Gillberg, C., Leboyer, M., Bourgeron, T., and Paris Autism Research International Sibpair, S. (2002). Linkage and association of the glutamate receptor 6 gene with autism. Molecular psychiatry 7, 302-310.

Johannessen, C.U. (2000). Mechanisms of action of valproate: a commentatory. Neurochem Int 37, 103-110.

Johannessen Landmark, C. (2008). Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 22, 27-47.

Joosten, A.V., and Bundy, A.C. (2010). Sensory processing and stereotypical and repetitive behaviour in children with autism and intellectual disability. Aust Occup Ther J 57, 366-372.

Kahne, D., Tudorica, A., Borella, A., Shapiro, L., Johnstone, F., Huang, W., and Whitaker-Azmitia, P.M. (2002). Behavioral and magnetic resonance spectroscopic studies in the rat hyperserotonemic model of autism. Physiology & behavior 75, 403-410.

Kalivas, P.W. (2009). The glutamate homeostasis hypothesis of addiction. Nature reviews Neuroscience 10, 561-572.

Kanner, L. (1968). Autistic disturbances of affective contact. Acta Paedopsychiatr 35, 100-136.

Kern, J.K., and Jones, A.M. (2006). Evidence of toxicity, oxidative stress, and neuronal insult in autism. Journal of toxicology and environmental health Part B, Critical reviews 9, 485-499.

Khan, M., Sekhon, B., Jatana, M., Giri, S., Gilg, A.G., Sekhon, C., Singh, I., and Singh, A.K. (2004). Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. Journal of neuroscience research 76, 519-527.

Kim, J.E., Lyoo, I.K., Estes, A.M., Renshaw, P.F., Shaw, D.W., Friedman, S.D., Kim, D.J., Yoon, S.J., Hwang, J., and Dager, S.R. (2010). Laterobasal amygdalar enlargement in 6- to 7-year-old children with autism spectrum disorder. Arch Gen Psychiatry 67, 1187-1197.

Kim, K.C., Kim, P., Go, H.S., Choi, C.S., Yang, S.I., Cheong, J.H., Shin, C.Y., and Ko, K.H. (2011). The critical period of valproate exposure to induce autistic symptoms in Sprague-Dawley rats. Toxicol Lett 201, 137-142.

Krettek, J.E., and Price, J.L. (1978). A description of the amygdaloid complex in the rat and cat with observations on intra-amygdaloid axonal connections. J Comp Neurol 178, 255-280.

Kulkarni, M.L., Zaheeruddin, M., Shenoy, N., and Vani, H.N. (2006). Fetal valproate syndrome. Indian J Pediatr 73, 937-939.

Lamb, J.A., Moore, J., Bailey, A., and Monaco, A.P. (2000). Autism: recent molecular genetic advances. Human molecular genetics 9, 861-868.

LeDoux, J. (2003). The emotional brain, fear, and the amygdala. Cellular and molecular neurobiology 23, 727-738.

Leskovec, T.J., Rowles, B.M., and Findling, R.L. (2008). Pharmacological treatment options for autism spectrum disorders in children and adolescents. Harv Rev Psychiatry 16, 97-112.

Lin, H.C., Gean, P.W., Wang, C.C., Chan, Y.H., and Chen, P.S. (2013). The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model. PloS one 8, e55248.

Lin, H.C., Mao, S.C., Su, C.L., and Gean, P.W. (2010). Alterations of excitatory transmission in the lateral amygdala during expression and extinction of fear memory. Int J Neuropsychopharmacol 13, 335-345.

Linden, A.M., Greene, S.J., Bergeron, M., and Schoepp, D.D. (2004). Anxiolytic activity of the MGLU2/3 receptor agonist LY354740 on the elevated plus maze is associated with the suppression of stress-induced c-Fos in the hippocampus and increases in c-Fos induction in several other stress-sensitive brain regions. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29, 502-513.

Luby, J., Mrakotsky, C., Stalets, M.M., Belden, A., Heffelfinger, A., Williams, M., and Spitznagel, E. (2006). Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy. J Child Adolesc Psychopharmacol 16, 575-587.

Mineur, Y.S., Sluyter, F., de Wit, S., Oostra, B.A., and Crusio, W.E. (2002). Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse. Hippocampus 12, 39-46.

Moldrich, R.X., Chapman, A.G., De Sarro, G., and Meldrum, B.S. (2003). Glutamate metabotropic receptors as targets for drug therapy in epilepsy. European journal of pharmacology 476, 3-16.

Moles, A., Kieffer, B.L., and D'Amato, F.R. (2004). Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science 304, 1983-1986.

Moreno-Fuenmayor, H., Borjas, L., Arrieta, A., Valera, V., and Socorro-Candanoza, L. (1996). Plasma excitatory amino acids in autism. Investigacion clinica 37, 113-128.

Mosconi, M.W., Cody-Hazlett, H., Poe, M.D., Gerig, G., Gimpel-Smith, R., and Piven, J. (2009). Longitudinal study of amygdala volume and joint attention in 2- to 4-year-old children with autism. Archives of general psychiatry 66, 509-516.

Muris, P., Steerneman, P., Merckelbach, H., Holdrinet, I., and Meesters, C. (1998). Comorbid anxiety symptoms in children with pervasive developmental disorders. J Anxiety Disord 12, 387-393.

Myers, S.M., and Johnson, C.P. (2007). Management of children with autism spectrum disorders. Pediatrics 120, 1162-1182.

Nanson, J.L. (1992). Autism in fetal alcohol syndrome: a report of six cases. Alcoholism, clinical and experimental research 16, 558-565.

Owen, R., Sikich, L., Marcus, R.N., Corey-Lisle, P., Manos, G., McQuade, R.D., Carson, W.H., and Findling, R.L. (2009). Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics 124, 1533-1540.

Pandina, G.J., Bossie, C.A., Youssef, E., Zhu, Y., and Dunbar, F. (2007). Risperidone improves behavioral symptoms in children with autism in a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 37, 367-373.

Parachikova, A., Vasilevko, V., Cribbs, D.H., LaFerla, F.M., and Green, K.N. (2010). Reductions in amyloid-beta-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation. Journal of Alzheimer's disease : JAD 21, 527-542.

Perry, W., Minassian, A., Lopez, B., Maron, L., and Lincoln, A. (2007). Sensorimotor gating deficits in adults with autism. Biol Psychiatry 61, 482-486.

Persico, A.M., and Bourgeron, T. (2006). Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 29, 349-358.

Perucca, E. (2002). Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs 16, 695-714.

Phiel, C.J., Zhang, F., Huang, E.Y., Guenther, M.G., Lazar, M.A., and Klein, P.S. (2001). Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. The Journal of biological chemistry 276, 36734-36741.

Purcell, A.E., Jeon, O.H., Zimmerman, A.W., Blue, M.E., and Pevsner, J. (2001). Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology 57, 1618-1628.

Rapin, I., and Tuchman, R.F. (2008). Autism: definition, neurobiology, screening, diagnosis. Pediatr Clin North Am 55, 1129-1146, viii.

Rasalam, A.D., Hailey, H., Williams, J.H., Moore, S.J., Turnpenny, P.D., Lloyd, D.J., and Dean, J.C. (2005). Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Developmental medicine and child neurology 47, 551-555.

Rodier, P.M., Ingram, J.L., Tisdale, B., and Croog, V.J. (1997). Linking etiologies in humans and animal models: studies of autism. Reproductive toxicology 11, 417-422.

Rosenberg, G. (2007). The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci 64, 2090-2103.

Rubenstein, J.L., and Merzenich, M.M. (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, brain, and behavior 2, 255-267.

Rutter, M. (2005). Incidence of autism spectrum disorders: changes over time and their meaning. Acta paediatrica 94, 2-15.

Schneider, M., and Koch, M. (2005). Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 30, 944-957.

Schneider, T., and Przewlocki, R. (2005). Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 30, 80-89.

Shigemoto, R., Kinoshita, A., Wada, E., Nomura, S., Ohishi, H., Takada, M., Flor, P.J., Neki, A., Abe, T., Nakanishi, S., et al. (1997). Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 17, 7503-7522.

Shinohe, A., Hashimoto, K., Nakamura, K., Tsujii, M., Iwata, Y., Tsuchiya, K.J., Sekine, Y., Suda, S., Suzuki, K., Sugihara, G., et al. (2006). Increased serum levels of glutamate in adult patients with autism. Progress in neuro-psychopharmacology & biological psychiatry 30, 1472-1477.

Sparks, B.F., Friedman, S.D., Shaw, D.W., Aylward, E.H., Echelard, D., Artru, A.A., Maravilla, K.R., Giedd, J.N., Munson, J., Dawson, G., et al. (2002). Brain structural abnormalities in young children with autism spectrum disorder. Neurology 59, 184-192.

Stromland, K., Nordin, V., Miller, M., Akerstrom, B., and Gillberg, C. (1994). Autism in thalidomide embryopathy: a population study. Dev Med Child Neurol 36, 351-356.

Su, A.I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K.A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004). A gene atlas of the mouse and human protein-encoding transcriptomes. Proceedings of the National Academy of Sciences of the United States of America 101, 6062-6067.

Tang, E., Yip, P.K., Chapman, A.G., Jane, D.E., and Meldrum, B.S. (1997). Prolonged anticonvulsant action of glutamate metabotropic receptor agonists in inferior colliculus of genetically epilepsy-prone rats. European journal of pharmacology 327, 109-115.

Tirouvanziam, R., Obukhanych, T.V., Laval, J., Aronov, P.A., Libove, R., Banerjee, A.G., Parker, K.J., O'Hara, R., Herzenberg, L.A., Herzenberg, L.A., et al. (2012). Distinct plasma profile of polar neutral amino acids, leucine, and glutamate in children with Autism Spectrum Disorders. Journal of autism and developmental disorders 42, 827-836.

Toal, F., Daly, E.M., Page, L., Deeley, Q., Hallahan, B., Bloemen, O., Cutter, W.J., Brammer, M.J., Curran, S., Robertson, D., et al. (2010). Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study. Psychol Med 40, 1171-1181.

Wagner, G.C., Reuhl, K.R., Cheh, M., McRae, P., and Halladay, A.K. (2006). A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate. J Autism Dev Disord 36, 779-793.

Wall, D.P., Esteban, F.J., Deluca, T.F., Huyck, M., Monaghan, T., Velez de Mendizabal, N., Goni, J., and Kohane, I.S. (2009). Comparative analysis of neurological disorders focuses genome-wide search for autism genes. Genomics 93, 120-129.

Walsh, R.N., and Cummins, R.A. (1976). The Open-Field Test: a critical review. Psychological bulletin 83, 482-504.

Wang, A.T., Dapretto, M., Hariri, A.R., Sigman, M., and Bookheimer, S.Y. (2004). Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 43, 481-490.

Webb, S.J., Sparks, B.F., Friedman, S.D., Shaw, D.W., Giedd, J., Dawson, G., and Dager, S.R. (2009). Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder. Psychiatry Res 172, 61-67.

Wieronska, J.M., Szewczyk, B., Palucha, A., Branski, P., Zieba, B., and Smialowska, M. (2005). Anxiolytic action of group II and III metabotropic glutamate receptors agonists involves neuropeptide Y in the amygdala. Pharmacological reports : PR 57, 734-743.

Williams, G., King, J., Cunningham, M., Stephan, M., Kerr, B., and Hersh, J.H. (2001). Fetal valproate syndrome and autism: additional evidence of an association. Developmental medicine and child neurology 43, 202-206.

Winslow, J.T., Hearn, E.F., Ferguson, J., Young, L.J., Matzuk, M.M., and Insel, T.R. (2000). Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse. Hormones and behavior 37, 145-155.

Wyszynski, D.F., Nambisan, M., Surve, T., Alsdorf, R.M., Smith, C.R., Holmes, L.B., and Antiepileptic Drug Pregnancy, R. (2005). Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 64, 961-965.

Yizhar, O., Fenno, L.E., Prigge, M., Schneider, F., Davidson, T.J., O'Shea, D.J., Sohal, V.S., Goshen, I., Finkelstein, J., Paz, J.T., et al. (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477, 171-178.

Zanchi, A.C., Saiki, M., Saldiva, P.H., Barros, H.M., and Rhoden, C.R. (2010). Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field. Inhalation toxicology 22, 84-88.

Zucker, R.S., and Regehr, W.G. (2002). Short-term synaptic plasticity. Annu Rev Physiol 64, 355-405.


連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 1.富田芳郎著,粵華譯,〈臺灣鄉鎮之研究〉 《臺灣銀行季刊》,第7卷第3期,1956年。
2. 3.郭海鳴,〈清代以前臺灣土地之開墾〉 《臺灣文獻》,第9卷第2期,1958年。
3. 4.張勝彥,〈清代臺灣漢人土地所有型態之研究〉 《臺灣文獻》,第34卷第2期,1983年。
4. 5.張勝彥,〈清代臺灣漢人土地所有型態之研究〉《臺灣文獻》,第34卷第2期,1983年。
5. 6.黃文博,〈臺南地區「五大香」之現況比較研究〉 ,《南瀛文獻》,第35期,1990年。
6. 7.黃秀娥‧黃振義,〈臺灣早期的土地開發和聚落發展—以臺南縣的發展和變遷為例〉 《雄中學報》,第2期,1992年。
7. 8.潘英,〈臺南縣拓殖史與其族系及姓氏〉《南瀛文獻》,第37期,1993年。
8. 11.陳敏璜,〈北門郡學甲庄大正七年(民國七年)學甲區沿革誌〉 ,《南瀛文獻》,第41卷,1996年。
9. 12.陳敏璜,〈日據時期北門郡概況〉 ,《南瀛文獻》,第41卷,1996年。
10. 14.蔡錦堂,〈日治時期臺灣之宗教政策〉,《歷史文化與台灣 臺灣研究研討會紀錄(70-100回)》,臺灣風物,1996年。
11. 16.趙文榮,〈由地名談區域拓殖的內在意涵--試以嘉南地區為例〉 《臺南文化》,第49期,2000年。
12. 19.謝國興,〈光復以來台南縣的產業發展概述〉,《南瀛文獻》第三輯,新營:台南縣政府,2004年。
13. 20.吳建昇,〈台江浮覆地的拓墾與「東八保」大道公信仰之研究〉 《臺南文化》,62,頁81-108,2008年。
14. 21.周俊霖,〈臺糖南北平行預備線在臺南縣的接軌工程〉,《南瀛文獻》,第6期,2008年。
 
1. 星途奇航~育有自閉症孩子之輕症自閉症者的父職實踐與自我調適
2. 國小自閉症、注意力缺陷過動症與一般學童在自閉症類群障礙檢核表之表現比較研究
3. 高功能自閉症學生高階心智理論教學之成效研究−以一名高職自閉症學生之心智解讀實驗教學為例
4. 探討自閉症兒童在融合班的學習經驗—以三個就讀竹師實小融合班的自閉症學生為例
5. 自閉症類群障礙症檢核表中文版信效度研究:以臺灣北部地區高功能自閉症類群障礙症學童為例
6. 自閉症類群障礙檢核表中文版信效度研究: 以臺灣北部地區自閉症類群障礙學童為例
7. 自閉症類疾患兒童的診斷穩定度、自閉症狀變化與認知及適應功能關係之縱貫研究
8. 自閉症兒童之正常手足生活適應研究-以台北縣自閉症服務協進會為例
9. 自閉症類疾患兒童自閉症狀變化與認知及適應行為關係之縱貫研究
10. 學齡前自閉症類群疾患兒童母親親職壓力相關因素:問題行為、自閉症症狀嚴重度
11. 泛自閉症兒童及青少年的手足:廣泛自閉症表現型特質與其生活適應
12. 修訂版學步期自閉症檢核表(M-CHAT)篩檢4歲以下自閉症類群疾患兒童效度探究
13. 自閉症患者家長之廣泛自閉症表現型及親職壓力與因應
14. 社會世界如何形塑自閉症者的自我認知─ 以台灣戰後的自閉症為例(1967-2013)
15. 對話式閱讀提升國小重度自閉症兒童口語表達之行動研究