Please use this identifier to cite or link to this item:
https://ah.lib.nccu.edu.tw/handle/140.119/71001| 題名: | 第五型類细胞週期蛋白依賴型激酶缺失小鼠的神經化學與行為表型分析 Behavioral and neurochemical phenotyping in mice lacking cyclin-dependent kinase-like 5 (CDKL5) |
作者: | 高方淇 | 貢獻者: | 廖文霖 高方淇 |
關鍵詞: | 自閉症 注意力不足過動症 第五型類细胞週期蛋白依賴激酶 多巴胺 紋狀體 前額皮質 ASD ADHD CDKL5 dopamine striatum medial prefrontal cortex |
日期: | 2013 | 上傳時間: | 3-Nov-2014 | 摘要: | 第五型類细胞週期蛋白依賴激酶(Cyclin-dependent kinase like 5, CDKL5)為一種絲胺酸/蘇胺酸蛋白磷酸激酶。此基因之突變會造成許多神經發育疾病，其中包含泛自閉障礙 (autism spectrum disorders, ASD)。為了瞭解CDKL5基因突變所造成的大腦與行為改變，本研究進行Cdkl5缺失小鼠的行為表型與神經化學分析。我們首先檢測缺少CDKL5是否造成泛自閉障礙之行為表徵，結果發現Cdkl5基因剔除小鼠表現較明顯的重複性挖掘墊料之刻板行為，並且明顯花費較少時間與陌生小鼠互動，顯示其在社會互動與社交偏好之能力有所缺失。此外，測量母鼠誘發之超音波鳴叫 (ultrasonic vocalization)發現，Cdkl5基因剔除小鼠產生較少的總鳴叫次數與時間，顯示其社交溝通之能力之障礙。值得注意的是，Cdkl5基因剔除小鼠之敞箱活動力遠高於野生型小鼠。有鑑於泛自閉障礙與注意力不足過動症(Attention deficit hyperactivity disorder, ADHD)之間的高共病率，因此我們檢驗Cdkl5基因剔除小鼠是否也表現ADHD之其他行為表徵。結果顯示，突變鼠相較於正常鼠有較高的衝動性與攻擊行為，且在空間學習的認知表現中有較差的學習曲線，可能是由於注意力異常所導致。我們進一步檢測Cdkl5基因剔除小鼠腦中神經化學的改變，發現其在紋狀體與前額皮質的多巴胺含量有明顯改變，並伴隨相應之多巴胺合成酶與代謝酶蛋白質含量之變化。此外，我們也發現Cdkl5基因剔除小鼠在ASD與ADHD相關蛋白質的表現量隨腦區而有不同程度的差異。最後，我們測試目前廣泛用於治療ADHD患者的心理興奮劑利他能是否可以改善Cdkl5基因剔除小鼠之行為症狀，發現此藥物可能藉由增加前腦多巴胺的含量進而改善Cdkl5突變小鼠之過動與刻板行為。綜上所述，本研究探討了CDKL5缺失在多巴胺系統上的影響，並提供一個ASD與 ADHD共病之動物模式，可望成為未來藥物篩選之平台。 | 參考文獻: | American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC\r\n\r\nAmara, S.G. & Kuhar, M.J. (1993) Neurotransmitter transporters: recent progress. Annual review of neuroscience, 16, 73-93.\r\n\r\nAmendola, E., Zhan, Y., Mattucci, C., Castroflorio, E., Calcagno, E., Fuchs, C., Lonetti, G., Silingardi, D., Vyssotski, A.L. & Farley, D. (2014) Mapping Pathological Phenotypes in a Mouse Model of CDKL5 Disorder. PloS one, 9, e91613.\r\n\r\nApplegate, B., Lahey, B.B., Hart, E.L., Biederman, J., Hynd, G.W., Barkley, R.A., Ollendick, T., Frick, P.J., GREENHILI, L. & McBurnett, K. (1997) Validity of the age-of-onset criterion for ADHD: a report from the DSM-IV field trials. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 1211-1221.\r\n\r\nAvale, M., Falzone, T., Gelman, D., Low, M., Grandy, D. & Rubinstein, M. (2003) The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Molecular psychiatry, 9, 718-726.\r\n\r\nAvale, M., Falzone, T., Gelman, D., Low, M., Grandy, D. & Rubinstein, M. (2004) The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Molecular psychiatry, 9, 718-726.\r\n\r\nBahi-Buisson, N., Nectoux, J., Rosas-Vargas, H., Milh, M., Boddaert, N., Girard, B., Cances, C., Ville, D., Afenjar, A. & Rio, M. (2008) Key clinical features to identify girls with CDKL5 mutations. Brain, 131, 2647-2661.\r\n\r\nBarnes, C.A. (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. Journal of comparative and physiological psychology, 93, 74.\r\n\r\nBlundell, J., Blaiss, C.A., Etherton, M.R., Espinosa, F., Tabuchi, K., Walz, C., Bolliger, M.F., Südhof, T.C. & Powell, C.M. (2010) Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. The Journal of Neuroscience, 30, 2115-2129.\r\n\r\nBotchin, M.B., Kaplan, J.R., Manuck, S.B. & Mann, J.J. (1993) Low versus high prolactin responders to fenfluramine challenge: marker of behavioral differences in adult male cynomolgus macaques. Neuropsychopharmacology, 9, 93-99.\r\n\r\nBrozoski, T.J., Brown, R.M., Rosvold, H. & Goldman, P.S. (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science, 205, 929-932.\r\n\r\nBurgdorf, J. & Panksepp, J. (2006) The neurobiology of positive emotions. Neuroscience & Biobehavioral Reviews, 30, 173-187.\r\n\r\nButcher, S., Liptrot, J. & Aburthnott, G. (1991) Characterisation of methylphenidate and nomifensine induced dopamine release in rat striatum using in vivo brain microdialysis. Neuroscience letters, 122, 245-248.\r\n\r\nCaron, M.G. (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 379, 15.\r\n\r\nCases, O., Seif, I., Grimsby, J., Gaspar, P., Chen, K., Pournin, S., Müller, U., Aguet, M., Babinet, C. & Shih, J.C. (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science (New York, NY), 268, 1763.\r\n\r\nCastellanos, F.X., Lee, P.P., Sharp, W., Jeffries, N.O., Greenstein, D.K., Clasen, L.S., Blumenthal, J.D., James, R.S., Ebens, C.L. & Walter, J.M. (2002) Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. Jama, 288, 1740-1748.\r\n\r\nChahrour, M. & Zoghbi, H.Y. (2007) The story of Rett syndrome: from clinic to neurobiology. Neuron, 56, 422-437.\r\n\r\nChen, Q., Zhu, Y.-C., Yu, J., Miao, S., Zheng, J., Xu, L., Zhou, Y., Li, D., Zhang, C. & Tao, J. (2010) CDKL5, a protein associated with Rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. The Journal of Neuroscience, 30, 12777-12786.\r\n\r\nChubykin, A.A., Liu, X., Comoletti, D., Tsigelny, I., Taylor, P. & Südhof, T.C. (2005) Dissection of synapse induction by neuroligins effect of a neuroligin mutation associated with autism. Journal of Biological Chemistry, 280, 22365-22374.\r\n\r\nChudasama, Y. & Robbins, T. (2006) Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and humans. Biological psychology, 73, 19-38.\r\n\r\nCostantini, F. & D’Amato, F.R. (2006) Ultrasonic vocalizations in mice and rats: social contexts and functions. Acta Zoologica Sinica, 52, 619-633.\r\n\r\nDastur, F.N., McGregor, I.S. & Brown, R.E. (1999) Dopaminergic modulation of rat pup ultrasonic vocalizations. European journal of pharmacology, 382, 53-67.\r\n\r\nDavidson, R.J., Putnam, K.M. & Larson, C.L. (2000) Dysfunction in the neural circuitry of emotion regulation--a possible prelude to violence. Science, 289, 591-594.\r\n\r\nDougherty, D.D., Bonab, A.A., Spencer, T.J., Rauch, S.L., Madras, B.K. & Fischman, A.J. (1999) Dopamine transporter density in patients with attention deficit hyperactivity disorder. The Lancet, 354, 2132-2133.\r\n\r\nDunnett, S.B. & Lelos, M. (2010) Behavioral analysis of motor and non-motor symptoms in rodent models of Parkinson’s disease. Progress in brain research, 184, 35-51.\r\n\r\nEnard, W. (2011) FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution. Current opinion in neurobiology, 21, 415-424.\r\n\r\nFaraone, S. & Biederman, J. (2002) Pathophysiology of attention-deficit/hyperactivity disorder. Neuropsychopharmacology: The Fifth Generation of Progress (Davis KL, Charney D, Coyle JT, Nemeroff C, eds). Philadelphia: Lippincott Williams & Wilkins, 577-596.\r\n\r\nFloresco, S.B. & Magyar, O. (2006) Mesocortical dopamine modulation of executive functions: beyond working memory. Psychopharmacology, 188, 567-585.\r\n\r\nFolstein, S.E. & Rosen-Sheidley, B. (2001) Genetics of austim: complex aetiology for a heterogeneous disorder. Nature Reviews Genetics, 2, 943-955.\r\n\r\nFombonne, E. (2004) Epidemiology of autistic disorder and other pervasive developmental disorders. The Journal of clinical psychiatry, 66, 3-8.\r\n\r\nFujita, E., Tanabe, Y., Shiota, A., Ueda, M., Suwa, K., Momoi, M.Y. & Momoi, T. (2008) Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells. Proceedings of the National Academy of Sciences, 105, 3117-3122.\r\n\r\nGainetdinov, R.R., Wetsel, W.C., Jones, S.R., Levin, E.D., Jaber, M. & Caron, M.G. (1999) Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science, 283, 397-401.\r\n\r\nGatley, S.J., Pan, D., Chen, R., Chaturvedi, G. & Ding, Y.-S. (1996) Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters. Life sciences, 58, PL231-PL239.\r\n\r\nGerasimov, M.R., Franceschi, M., Volkow, N.D., Gifford, A., Gatley, S.J., Marsteller, D., Molina, P.E. & Dewey, S.L. (2000) Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. Journal of Pharmacology and Experimental Therapeutics, 295, 51-57.\r\n\r\nGumulka, W., Samanin, R., Garattini, S. & Valzelli, L. (1969) Effect of stimulation of midbrain raphe on serotonin (5-HT) level and turnover in different areas of rat brain. European journal of pharmacology, 8, 380-384.\r\n\r\nHamilton, P.J., Campbell, N.G., Sharma, S., Erreger, K., Hansen, F.H., Saunders, C., Belovich, A.N., Daly, M., Gibbs, R. & Boerwinkle, E. (2013) De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. Molecular psychiatry, 18, 1315-1323.\r\n\r\nHarrison, A.A., Everitt, B.J. & Robbins, T.W. (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology, 133, 329-342.\r\n\r\nHigley, J., Hasert, M., Suomi, S. & Linnoila, M. (1998) The serotonin reuptake inhibitor sertraline reduces excessive alcohol consumption in nonhuman primates: effect of stress. Neuropsychopharmacology, 18, 431-443.\r\n\r\nHurd, Y.L. & Ungerstedt, U. (1989) In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudate-putamen. European journal of pharmacology, 166, 251-260.\r\n\r\nHurst, J.A., Baraitser, M., Auger, E., Graham, F. & Norell, S. (1990) An extended family with a dominantly inherited speech disorder. Developmental Medicine & Child Neurology, 32, 352-355.\r\n\r\nIkemoto, S. (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex. Brain research reviews, 56, 27-78.\r\n\r\nJaber, M., Dumartin, B., Sagné, C., Haycock, J.W., Roubert, C., Giros, B., Bloch, B. & Caron, M.G. (1999) Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. European Journal of Neuroscience, 11, 3499-3511.\r\n\r\nJamain, S., Quach, H., Betancur, C., Råstam, M., Colineaux, C., Gillberg, I.C., Soderstrom, H., Giros, B., Leboyer, M. & Gillberg, C. (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature genetics, 34, 27-29.\r\n\r\nJamain, S., Radyushkin, K., Hammerschmidt, K., Granon, S., Boretius, S., Varoqueaux, F., Ramanantsoa, N., Gallego, J., Ronnenberg, A. & Winter, D. (2008) Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proceedings of the National Academy of Sciences, 105, 1710-1715.\r\n\r\nKalscheuer, V.M., Tao, J., Donnelly, A., Hollway, G., Schwinger, E., Kübart, S., Menzel, C., Hoeltzenbein, M., Tommerup, N. & Eyre, H. (2003) Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. The American Journal of Human Genetics, 72, 1401-1411.\r\n\r\nKaplan, J.R., Fontenot, M.B., Berard, J., Manuck, S.B. & Mann, J.J. (1995) Delayed dispersal and elevated monoaminergic activity in free‐ranging rhesus monkeys. American Journal of Primatology, 35, 229-234.\r\n\r\nKogan, M.D., Blumberg, S.J., Schieve, L.A., Boyle, C.A., Perrin, J.M., Ghandour, R.M., Singh, G.K., Strickland, B.B., Trevathan, E. & van Dyck, P.C. (2009) Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics, 124, 1395-1403.\r\n\r\nKramer, U., Chi, C.S., Lin, K.L., Specchio, N., Sahin, M., Olson, H., Nabbout, R., Kluger, G., Lin, J.J. & van Baalen, A. (2011) Febrile infection–related epilepsy syndrome (FIRES): Pathogenesis, treatment, and outcome. Epilepsia, 52, 1956-1965.\r\n\r\nKrause, K.-H., Dresel, S.H., Krause, J., Kung, H.F. & Tatsch, K. (2000) Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography. Neuroscience letters, 285, 107-110.\r\n\r\nKuczenski, R. & Segal, D.S. (1997) Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. Journal of neurochemistry, 68, 2032-2037.\r\n\r\nKuczenski, R., Segal, D.S. & Aizenstein, M. (1991) Amphetamine, cocaine, and fencamfamine: relationship between locomotor and stereotypy response profiles and caudate and accumbens dopamine dynamics. The Journal of neuroscience, 11, 2703-2712.\r\n\r\nLai, C.S., Fisher, S.E., Hurst, J.A., Vargha-Khadem, F. & Monaco, A.P. (2001) A forkhead-domain gene is mutated in a severe speech and language disorder. Nature, 413, 519-523.\r\n\r\nLai, C.S., Gerrelli, D., Monaco, A.P., Fisher, S.E. & Copp, A.J. (2003) FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder. Brain, 126, 2455-2462.\r\n\r\nLangen, M., Kas, M.J., Staal, W.G., van Engeland, H. & Durston, S. (2011) The neurobiology of repetitive behavior: of mice…. Neuroscience & Biobehavioral Reviews, 35, 345-355.\r\n\r\nLiao, W.-L., Tsai, H.-C., Wang, H.-F., Chang, J., Lu, K.-M., Wu, H.-L., Lee, Y.-C., Tsai, T.-F., Takahashi, H. & Wagner, M. (2008) Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proceedings of the National Academy of Sciences, 105, 6765-6770.\r\n\r\nLinnoila, V.M. & Virkkunen, M. (1992) Aggression, suicidality, and serotonin. Journal of Clinical Psychiatry.\r\n\r\nMcFadyen, M.P., Brown, R.E. & Carrey, N. (2002) Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice. Developmental psychobiology, 41, 123-132.\r\n\r\nMontini, E., Andolfi, G., Caruso, A., Buchner, G., Walpole, S.M., Mariani, M., Consalez, G., Trump, D., Ballabio, A. & Franco, B. (1998) Identification and characterization of a novel serine–threonine kinase gene from the Xp22 region. Genomics, 51, 427-433.\r\n\r\nMoy, S., Nadler, J., Perez, A., Barbaro, R., Johns, J., Magnuson, T., Piven, J. & Crawley, J. (2004) Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice. Genes, Brain and Behavior, 3, 287-302.\r\n\r\nNestler, E.J. & Hyman, S.E. (2010) Animal models of neuropsychiatric disorders. Nature neuroscience, 13, 1161-1169.\r\n\r\nNetter, P. & Rammsayer, T. (1991) Reactivity to dopaminergic drugs and aggression related personality traits. Personality and Individual Differences, 12, 1009-1017.\r\n\r\nNieoullon, A. (2002) Dopamine and the regulation of cognition and attention. Progress in neurobiology, 67, 53-83.\r\n\r\nNoaín, D., Avale, M.E., Wedemeyer, C., Calvo, D., Peper, M. & Rubinstein, M. (2006) Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice. European Journal of Neuroscience, 24, 2429-2438.\r\n\r\nPortfors, C.V. (2007) Types and functions of ultrasonic vocalizations in laboratory rats and mice. Journal of the American Association for Laboratory Animal Science, 46, 28-34.\r\n\r\nPotter, P., Wolf, L., Boxerman, S., Grayson, D., Sledge, J., Dunagan, C. & Evanoff, B. (2005) Understanding the cognitive work of nursing in the acute care environment. Journal of Nursing Administration, 35, 327-335.\r\n\r\nRao, P.A. & Landa, R.J. (2013) Association between severity of behavioral phenotype and comorbid attention deficit hyperactivity disorder symptoms in children with autism spectrum disorders. Autism, 1362361312470494.\r\n\r\nRaymond, L., Diebold, B., Leroux, C., Maurey, H., Drouin-Garraud, V., Delahaye, A., Dulac, O., Metreau, J., Melikishvili, G. & Toutain, A. (2013) Validation of high-resolution DNA melting analysis for mutation scanning of the< i> CDKL5</i> gene: Identification of novel mutations. Gene, 512, 70-75.\r\n\r\nRhodes, J. & Garland Jr, T. (2003) Differential sensitivity to acute administration of Ritalin, apormorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology, 167, 242-250.\r\n\r\nRhodes, J.S., van Praag, H., Jeffrey, S., Girard, I., Mitchell, G.S., Garland Jr, T. & Gage, F.H. (2003) Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behavioral neuroscience, 117, 1006.\r\n\r\nRobinson, T.E. & Camp, D.M. (1990) Does amphetamine preferentially increase the extracellular concentration of dopamine in the mesolimbic system of freely moving rats? Neuropsychopharmacology.\r\n\r\nRubenstein, J. & Merzenich, M. (2003) Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes, Brain and Behavior, 2, 255-267.\r\n\r\nRubenstein, J.L. (2010) Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder. Current opinion in neurology, 23, 118-123.\r\n\r\nRubia, K. (2002) The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia. Behavioural brain research, 130, 47-56.\r\n\r\nRusconi, L., Salvatoni, L., Giudici, L., Bertani, I., Kilstrup-Nielsen, C., Broccoli, V. & Landsberger, N. (2008) CDKL5 expression is modulated during neuronal development and its subcellular distribution is tightly regulated by the C-terminal tail. Journal of biological chemistry, 283, 30101-30111.\r\n\r\nRussell, V., de Villiers, A., Sagvolden, T., Lamm, M. & Taljaard, J. (1995) Altered dopaminergic function in the prefrontal cortex, nucleus accumbens and caudate-putamen of an animal model of attention-deficit hyperactivity disorder—the spontaneously hypertensive rat. Brain Research, 676, 343-351.\r\n\r\nSakai, Y., Shaw, C.A., Dawson, B.C., Dugas, D.V., Al-Mohtaseb, Z., Hill, D.E. & Zoghbi, H.Y. (2011) Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine, 3, 86ra49-86ra49.\r\n\r\nScattoni, M.L., Crawley, J. & Ricceri, L. (2009) Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 33, 508-515.\r\n\r\nScattoni, M.L., Ricceri, L. & Crawley, J.N. (2011) Unusual repertoire of vocalizations in adult BTBR T+ tf/J mice during three types of social encounters. Genes, Brain and Behavior, 10, 44-56.\r\n\r\nSchweri, M.M., Skolnick, P., Rafferty, M.F., Rice, K.C., Janowsky, A.J. & Paul, S.M. (1985) [3H] Threo‐(±)‐Methylphenidate Binding to 3, 4‐Dihydroxyphenylethylamine Uptake Sites in Corpus Striatum: Correlation with the Stimulant Properties of Ritalinic Acid Esters. Journal of neurochemistry, 45, 1062-1070.\r\n\r\nSekiguchi, M., Katayama, S., Hatano, N., Shigeri, Y., Sueyoshi, N. & Kameshita, I. (2013) Identification of amphiphysin 1 as an endogenous substrate for CDKL5, a protein kinase associated with X-linked neurodevelopmental disorder. Archives of biochemistry and biophysics, 535, 257-267.\r\n\r\nSeo, D., Patrick, C.J. & Kennealy, P.J. (2008) Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggression and violent behavior, 13, 383-395.\r\n\r\nSharp, T., Zetterström, T., Ljungberg, T. & Ungerstedt, U. (1987) A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis. Brain research, 401, 322-330.\r\n\r\nSong, J.-Y., Ichtchenko, K., Südhof, T.C. & Brose, N. (1999) Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proceedings of the National Academy of Sciences, 96, 1100-1105.\r\n\r\nStaal, W.G., de Krom, M. & de Jonge, M.V. (2012) Brief report: the dopamine-3-receptor gene (DRD3) is associated with specific repetitive behavior in autism spectrum disorder (ASD). Journal of autism and developmental disorders, 42, 885-888.\r\n\r\nSzechtman, H., Ornstein, K., Teitelbaum, P. & Golani, I. (1985) The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat. Neuroscience, 14, 783-798.\r\n\r\nTabuchi, K., Blundell, J., Etherton, M.R., Hammer, R.E., Liu, X., Powell, C.M. & Südhof, T.C. (2007) A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. science, 318, 71-76.\r\n\r\nTalkowski, M.E., Rosenfeld, J.A., Blumenthal, I., Pillalamarri, V., Chiang, C., Heilbut, A., Ernst, C., Hanscom, C., Rossin, E. & Lindgren, A.M. (2012) Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell, 149, 525-537.\r\n\r\nTurjanski, N., Lees, A. & Brooks, D. (1999) Striatal dopaminergic function in restless legs syndrome 18F-dopa and 11C-raclopride PET studies. Neurology, 52, 932-932.\r\n\r\nValli, E., Trazzi, S., Fuchs, C., Erriquez, D., Bartesaghi, R., Perini, G. & Ciani, E. (2012) CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1819, 1173-1185.\r\n\r\nVaroqueaux, F., Jamain, S. & Brose, N. (2004) Neuroligin 2 is exclusively localized to inhibitory synapses. European journal of cell biology, 83, 449-456.\r\n\r\nVattikuti, S. & Chow, C.C. (2010) A computational model for cerebral cortical dysfunction in autism spectrum disorders. Biological psychiatry, 67, 672-678.\r\n\r\nWang, I.-T.J., Allen, M., Goffin, D., Zhu, X., Fairless, A.H., Brodkin, E.S., Siegel, S.J., Marsh, E.D., Blendy, J.A. & Zhou, Z. (2012) Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice. Proceedings of the National Academy of Sciences, 109, 21516-21521.\r\n\r\nWeaving, L.S., Christodoulou, J., Williamson, S.L., Friend, K.L., McKenzie, O.L., Archer, H., Evans, J., Clarke, A., Pelka, G.J. & Tam, P.P. (2004) Mutations of< i> CDKL5</i> Cause a Severe Neurodevelopmental Disorder with Infantile Spasms and Mental Retardation. The American Journal of Human Genetics, 75, 1079-1093.\r\n\r\nWilliamson, S.L., Giudici, L., Kilstrup-Nielsen, C., Gold, W., Pelka, G.J., Tam, P.P., Grimm, A., Prodi, D., Landsberger, N. & Christodoulou, J. (2012) A novel transcript of cyclin-dependent kinase-like 5 (CDKL5) has an alternative C-terminus and is the predominant transcript in brain. Human genetics, 131, 187-200.\r\n\r\nWise, R.A. (2004) Dopamine, learning and motivation. Nature reviews neuroscience, 5, 483-494.\r\n\r\nZametkin, A.J. & Rapoport, J. (1987) Noradrenergic hypothesis of attention deficit disorder with hyperactivity: a critical review. Psychopharmacology: The third generation of progress, 837-842.\r\n\r\nZhu, Y.-C., Li, D., Wang, L., Lu, B., Zheng, J., Zhao, S.-L., Zeng, R. & Xiong, Z.-Q. (2013) Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development. Proceedings of the National Academy of Sciences, 110, 9118-9123. | 描述: | 碩士 國立政治大學 神經科學研究所 101754002 102 |
資料來源: | http://thesis.lib.nccu.edu.tw/record/#G0101754002 | 資料類型: | thesis |
| Appears in Collections: | 學位論文 |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| index.html | 128 B | HTML2 | View/Open |
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.