(3.238.173.209) 您好!臺灣時間:2021/05/09 16:07
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:李慧宇
研究生(外文):Wai-Yu Li
論文名稱:產前感染及社交隔離對於成年子代中腦─前額葉系統的影響
論文名稱(外文):The Effects of Prenatal Infection and Postweaning Social Isolation on the Mesocortical System in Adult Offspring
指導教授:李立仁李立仁引用關係
口試委員:賴文崧王培育李俊賢
口試日期:2013-07-15
學位類別:碩士
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:2013
畢業學年度:101
語文別:英文
論文頁數:66
中文關鍵詞:Poly I:C中前額葉皮質第二、三層錐體神經元樹突形態認知功能
外文關鍵詞:Poly I:Cmedial prefrontal cortex (mPFC)layer II/III pyramidal neuronsdendritic morphologycognitive function
相關次數:
  • 被引用被引用:0
  • 點閱點閱:101
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
母體在懷孕期間受到感染已被定義為一些神經發育精神疾病如:精神分裂症及自閉症的風險因子之一。此外, 越來越多的實驗證據顯示不良的生活經驗如:早期社會隔離會與這些精神病的發生息息相關。因此,我們想要研究兩個精神疾病的風險因子──產前感染及社交隔離,是否會互相作用,從而引發成年子代的行為異常及其中腦─前額葉多巴胺系統中神經元的改變。在本篇實驗中,我們對C57BL/6 背景的懷孕母鼠在其懷孕第九天時分別施打20mg/kg的polyriboinosinic: polyribocytidilic acid (poly I:C)以模擬產前病毒感染,待其生下後代並在其後代離乳後(約出生後30天),分為兩個組別,一組為集體飼養(3-5隻一籠),另一組為個別隔離飼養(1隻一籠)以模擬社交隔離,飼養一個月後,進行實驗去檢測四個組別的表現型。在行為方面,我們發現產前poly I:C處理小鼠在曠野實驗(open field test)中呈現活動力下降的情形,然而是否有社交隔離對此並沒影響。另一方面,與對照組相比,產前poly I:C處理及單獨飼養小鼠的短期記憶及前脈衝抑制 (Prepulse inhibition ; PPI) 有缺失的情況,顯示產前感染及社交隔離會對子代成年時期的行為造成影響。在組織學上,我們發現經過poly I:C處理的小鼠其腹側被蓋區 (Ventral tegmental area ; VTA) 中多巴胺神經細胞密度顯著增加,表示poly I:C處理後,後代的多巴胺系統出現異常。然而,抑制性神經細胞在前額葉皮質中的密度則只有在社交隔離小鼠上有顯著減少的情狀,代表產前感染及社交隔離分別影響後代不同的大腦系統。在神經形態方面,我們發現所有實驗組別的小鼠,其中前額葉皮質中第二、三層錐體神經元的基底樹突複雜性有所改變且其樹突棘的密度有顯著下降。總括以上實驗結果,產前感染結合社交隔離的小鼠出現認知功能下降及中前額葉皮質神經元結構上的改變,因此可以作為神經發育相關的精神疾病的動物模型。

Maternal infection during pregnancy is a noticed risk factor for neurodevelopment psychiatric disorders, such as schizophrenia and autism. Accumulating evidence suggests that adverse life experiences such as social isolation have been associated with the onset of psychosis. Therefore, our study aimed to test whether prenatal infection could interact with postweaning social isolation to induce behavioral deficits and neuronal alterations in the mesocortical dopamine system. In the present study, we treated the pregnant mice of C57BL/6 background with a single injection of polyriboinosinic: polyribocytidilic acid (Poly I:C, 20 mg/kg, i.p.) at gestation day 9 to mimic prenatal infection. After weaning at postnatal day P30, male offspring were reared individually to mimic social isolation or in group (3-5). Phenotypes were characterized in various aspects after P60. In the behavioral aspect, only poly I:C-offspring exhibited hypolocomotor activity in a novel open field but not in isolated-mice. Notably, impairment of short-term memory function tested in novel-object recognition task and prepulse inhibition deficits were found in all experiment groups compared to the control group. The number of dopaminergic neurons in the ventral tegmental area (VTA) was increased in poly I:C-offspring whereas the number of parvalbumin-expressing neurons in the medial prefrontal cortex (mPFC) was decreased in isolated-offspring. Histologically, the dendritic architecture of the layer II/III pyramidal neurons in the mPFC was examined. Alterations in dendritic complexity and reduced spine density were present in all experiment groups. Together, our data demonstrated that prenatal infection combined with postweaning social isolation lead to cognitive deficits and neuronal alteration, thus, it could be a model for neurodevelopment psychiatric disorders.

中文摘要 i
Abstract iii
Contents v
List of Figures viii
List of Tables ix
Abbreviations x

Chapter 1 Introduction 1
1.1 Schizophrenia and its causes 1
1.2 Dopamine hypotheses of Schizophrenia 2
1.3 Animal model of Schizophrenia 4
1.3.1 Animal model: Prenatal infection 4
1.3.2 Animal model: Social isolation 6

Chapter 2 Materials and Methods 8
2.1 Animals 8
2.2 Behavioral tests 9
2.2.1 Open field test (OFT) 9
2.2.2 Novel object recognition test (NORT) 10
2.2.3 Social Interaction test 11
2.2.4 Prepulse inhibition test (PPI) 12
2.3 Histology 14
2.3.1 Perfusion 14
2.3.2 Immunohistochemistry (IHC) 14
2.3.3 Golgi-Cox impregnation and morphometric analyses 17
2.4 Statistical analysis 18

Chapter 3 Results 19
3.1 Behavior Tests 19
3.1.1 Poly I:C-offspring exhibited hypolocomotor activity but not in isolated mice 19
3.1.2 Poly I:C-isolated mice exhibited impaired short-term memory function in novel object recognition test 20
3.1.3 No significant difference in social affiliation and sociability between four groups 21
3.1.4 Effects of prenatal infection and social isolation on sensorimotor
gating 22
3.2 Histology 23
3.2.1 Independent effects of prenatal infection and social isolation on dopamine neurons in the VTA 23
3.2.2 Independent effects of prenatal infection and social isolation on Parvalbumin-expressing interneurons in the mPFC 24
3.2.3 No effects of prenatal infection and social isolation on mature oligodendrocytes in the mPFC 24
3.3 Morphological analysis 21
3.3.1 Effects of prenatal infection and social isolation on the dendritic architectures of layer II/III mPFC pyramidal neurons 25
3.3.2 Effects of prental infection and social isolation on spine density in neurons of the mPFC 26

Chapter 4 Discussion 27

Reference 58




Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (2008) Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature genetics 40:827-834.
Alquicer G, Morales-Medina JC, Quirion R, Flores G (2008) Postweaning social isolation enhances morphological changes in the neonatal ventral hippocampal lesion rat model of psychosis. Journal of chemical neuroanatomy 35:179-187.
Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cognitive processing 13:93-110.
Baharnoori M, Brake WG, Srivastava LK (2009) Prenatal immune challenge induces developmental changes in the morphology of pyramidal neurons of the prefrontal cortex and hippocampus in rats. Schizophrenia research 107:99-109.
Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacological reviews 35:53-68.
Bertolucci-D''Angio M, Serrano A, Scatton B (1990) Mesocorticolimbic dopaminergic systems and emotional states. Journal of neuroscience methods 34:135-142.
Bianchi M, Fone KF, Azmi N, Heidbreder CA, Hagan JJ, Marsden CA (2006) Isolation rearing induces recognition memory deficits accompanied by cytoskeletal alterations in rat hippocampus. The European journal of neuroscience 24:2894-2902.
Bjorklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends in neurosciences 30:194-202.
Boksa P (2010) Effects of prenatal infection on brain development and behavior: a review of findings from animal models. Brain, behavior, and immunity 24:881-897.
Braff DL, Geyer MA, Swerdlow NR (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156:234-258.
Brown AS (2006) Prenatal infection as a risk factor for schizophrenia. Schizophrenia bulletin 32:200-202.
Brown AS (2012) Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Developmental neurobiology 72:1272-1276.
Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, Babulas VP, Susser ES (2004) Serologic evidence of prenatal influenza in the etiology of schizophrenia. Archives of general psychiatry 61:774-780.
Brown AS, Derkits EJ (2010) Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. The American journal of psychiatry 167:261-280.
Brown AS, Patterson PH (2011) Maternal infection and schizophrenia: implications for prevention. Schizophrenia bulletin 37:284-290.
Brown AS, Schaefer CA, Quesenberry CP, Jr., Liu L, Babulas VP, Susser ES (2005) Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. The American journal of psychiatry 162:767-773.
Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Wagner RL, Yolken RH (2001) Maternal cytokine levels during pregnancy and adult psychosis. Brain, behavior, and immunity 15:411-420.
Cannon TD, van Erp TG, Bearden CE, Loewy R, Thompson P, Toga AW, Huttunen MO, Keshavan MS, Seidman LJ, Tsuang MT (2003) Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophrenia bulletin 29:653-669.
Caspi A, Moffitt TE (2006) Gene-environment interactions in psychiatry: joining forces with neuroscience. Nature reviews Neuroscience 7:583-590.
Chattopadhyaya B, Cristo GD (2012) GABAergic circuit dysfunctions in neurodevelopmental disorders. Frontiers in psychiatry / Frontiers Research Foundation 3:51.
Clarke MC, Tanskanen A, Huttunen M, Whittaker JC, Cannon M (2009) Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia. The American journal of psychiatry 166:1025-1030.
Connor CM, Dincer A, Straubhaar J, Galler JR, Houston IB, Akbarian S (2012) Maternal immune activation alters behavior in adult offspring, with subtle changes in the cortical transcriptome and epigenome. Schizophrenia research 140:175-184.
Day-Wilson KM, Jones DN, Southam E, Cilia J, Totterdell S (2006) Medial prefrontal cortex volume loss in rats with isolation rearing-induced deficits in prepulse inhibition of acoustic startle. Neuroscience 141:1113-1121.
Deslauriers J, Larouche A, Sarret P, Grignon S (2013) Combination of prenatal immune challenge and restraint stress affects prepulse inhibition and dopaminergic/GABAergic markers. Progress in neuro-psychopharmacology & biological psychiatry 45C:156-164.
Eyles D, Feldon J, Meyer U (2012) Schizophrenia: do all roads lead to dopamine or is this where they start? Evidence from two epidemiologically informed developmental rodent models. Translational psychiatry 2:e81.
Ferdman N, Murmu RP, Bock J, Braun K, Leshem M (2007) Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats. Behavioural brain research 180:174-182.
Fortier ME, Luheshi GN, Boksa P (2007) Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy. Behavioural brain research 181:270-277.
Geyer MA, Wilkinson LS, Humby T, Robbins TW (1993) Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biological psychiatry 34:361-372.
Gilmore JH, Fredrik Jarskog L, Vadlamudi S, Lauder JM (2004) Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29:1221-1229.
Heidbreder CA, Weiss IC, Domeney AM, Pryce C, Homberg J, Hedou G, Feldon J, Moran MC, Nelson P (2000) Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome. Neuroscience 100:749-768.
Heim C, Plotsky PM, Nemeroff CB (2004) Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 29:641-648.
Heinz A, Schlagenhauf F (2010) Dopaminergic dysfunction in schizophrenia: salience attribution revisited. Schizophrenia bulletin 36:472-485.
Howland JG, Cazakoff BN, Zhang Y (2012) Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy. Neuroscience 201:184-198.
Ibi D, Takuma K, Koike H, Mizoguchi H, Tsuritani K, Kuwahara Y, Kamei H, Nagai T, Yoneda Y, Nabeshima T, Yamada K (2008) Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. Journal of neurochemistry 105:921-932.
Ira E, Zanoni M, Ruggeri M, Dazzan P, Tosato S (2013) COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation. Journal of psychiatry & neuroscience : JPN 38:120178.
Ito HT, Smith SE, Hsiao E, Patterson PH (2010) Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring. Brain, behavior, and immunity 24:930-941.
Jaaro-Peled H, Ayhan Y, Pletnikov MV, Sawa A (2010) Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophrenia bulletin 36:301-313.
Jaaro-Peled H, Hayashi-Takagi A, Seshadri S, Kamiya A, Brandon NJ, Sawa A (2009) Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1. Trends in neurosciences 32:485-495.
Juan LW, Liao CC, Lai WS, Chang CY, Pei JC, Wong WR, Liu CM, Hwu HG, Lee LJ (2013) Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain. Brain structure & function.
Kirkpatrick B (2013) Understanding the physiology of schizophrenia. The Journal of clinical psychiatry 74:e05.
Kneeland RE, Fatemi SH (2013) Viral infection, inflammation and schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry 42:35-48.
Koike H, Ibi D, Mizoguchi H, Nagai T, Nitta A, Takuma K, Nabeshima T, Yoneda Y, Yamada K (2009) Behavioral abnormality and pharmacologic response in social isolation-reared mice. Behavioural brain research 202:114-121.
Laplante F, Zhang ZW, Huppe-Gourgues F, Dufresne MM, Vaucher E, Sullivan RM (2012) Cholinergic depletion in nucleus accumbens impairs mesocortical dopamine activation and cognitive function in rats. Neuropharmacology 63:1075-1084.
Laruelle M, Kegeles LS, Abi-Dargham A (2003) Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Annals of the New York Academy of Sciences 1003:138-158.
Laviolette SR (2007) Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia? Schizophrenia bulletin 33:971-981.
Levine JB, Youngs RM, MacDonald ML, Chu M, Leeder AD, Berthiaume F, Konradi C (2007) Isolation rearing and hyperlocomotion are associated with reduced immediate early gene expression levels in the medial prefrontal cortex. Neuroscience 145:42-55.
Li T, Stefansson H, Gudfinnsson E, Cai G, Liu X, Murray RM, Steinthorsdottir V, Januel D, Gudnadottir VG, Petursson H, Ingason A, Gulcher JR, Stefansson K, Collier DA (2004) Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype. Molecular psychiatry 9:698-704.
Lu L, Bao G, Chen H, Xia P, Fan X, Zhang J, Pei G, Ma L (2003) Modification of hippocampal neurogenesis and neuroplasticity by social environments. Experimental neurology 183:600-609.
Lukasz B, O''Sullivan NC, Loscher JS, Pickering M, Regan CM, Murphy KJ (2013) Peripubertal viral-like challenge and social isolation mediate overlapping but distinct effects on behaviour and brain interferon regulatory factor 7 expression in the adult Wistar rat. Brain, behavior, and immunity 27:71-79.
Mahurin RK, Velligan DI, Miller AL (1998) Executive-frontal lobe cognitive dysfunction in schizophrenia: a symptom subtype analysis. Psychiatry research 79:139-149.
Masana M, Santana N, Artigas F, Bortolozzi A (2012) Dopamine neurotransmission and atypical antipsychotics in prefrontal cortex: a critical review. Current topics in medicinal chemistry 12:2357-2374.
Maynard TM, Sikich L, Lieberman JA, LaMantia AS (2001) Neural development, cell-cell signaling, and the "two-hit" hypothesis of schizophrenia. Schizophrenia bulletin 27:457-476.
McLean S, Grayson B, Harris M, Protheroe C, Woolley M, Neill J (2010) Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats. J Psychopharmacol 24:57-63.
Mei L, Xiong WC (2008) Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nature reviews Neuroscience 9:437-452.
Meyer-Lindenberg A (2010) From maps to mechanisms through neuroimaging of schizophrenia. Nature 468:194-202.
Meyer U, Feldon J (2009) Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia. Psychopharmacology 206:587-602.
Meyer U, Feldon J, Dammann O (2011) Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatric research 69:26R-33R.
Meyer U, Feldon J, Fatemi SH (2009) In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders. Neuroscience and biobehavioral reviews 33:1061-1079.
Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J (2006) The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. The Journal of neuroscience : the official journal of the Society for Neuroscience 26:4752-4762.
Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J (2008) Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33:441-456.
Mirescu C, Peters JD, Gould E (2004) Early life experience alters response of adult neurogenesis to stress. Nature neuroscience 7:841-846.
Moller M, Du Preez JL, Emsley R, Harvey BH (2011) Isolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 21:471-483.
Muchimapura S, Mason R, Marsden CA (2003) Effect of isolation rearing on pre- and post-synaptic serotonergic function in the rat dorsal hippocampus. Synapse 47:209-217.
Murray RM, Lappin J, Di Forti M (2008) Schizophrenia: from developmental deviance to dopamine dysregulation. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 18 Suppl 3:S129-134.
Nakazawa K, Zsiros V, Jiang Z, Nakao K, Kolata S, Zhang S, Belforte JE (2012) GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 62:1574-1583.
Narayan S, Nakajima K, Sawa A (2013) DISC1: A Key Lead in Studying Cortical Development and Associated Brain Disorders. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.
Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nature neuroscience 13:1161-1169.
Niwa M, Kamiya A, Murai R, Kubo K, Gruber AJ, Tomita K, Lu L, Tomisato S, Jaaro-Peled H, Seshadri S, Hiyama H, Huang B, Kohda K, Noda Y, O''Donnell P, Nakajima K, Sawa A, Nabeshima T (2010) Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits. Neuron 65:480-489.
Norton N, Williams HJ, Owen MJ (2006) An update on the genetics of schizophrenia. Current opinion in psychiatry 19:158-164.
Pascual R, Zamora-Leon P, Catalan-Ahumada M, Valero-Cabre A (2007) Early social isolation decreases the expression of calbindin D-28k and dendritic branching in the medial prefrontal cortex of the rat. The International journal of neuroscience 117:465-476.
Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nature neuroscience 14:285-293.
Picchioni MM, Murray RM (2007) Schizophrenia. BMJ 335:91-95.
Rapoport JL, Addington AM, Frangou S, Psych MR (2005) The neurodevelopmental model of schizophrenia: update 2005. Molecular psychiatry 10:434-449.
Rushworth MF, Noonan MP, Boorman ED, Walton ME, Behrens TE (2011) Frontal cortex and reward-guided learning and decision-making. Neuron 70:1054-1069.
Saha S, Chant D, Welham J, McGrath J (2005) A systematic review of the prevalence of schizophrenia. PLoS medicine 2:e141.
Santosh S, Dutta Roy D, Kundu PS (2013) Psychopathology, cognitive function, and social functioning of patients with schizophrenia. East Asian archives of psychiatry : official journal of the Hong Kong College of Psychiatrists = Dong Ya jing shen ke xue zhi : Xianggang jing shen ke yi xue yuan qi kan 23:65-70.
Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. The Journal of neuroscience : the official journal of the Society for Neuroscience 23:297-302.
Silva-Gomez AB, Rojas D, Juarez I, Flores G (2003) Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats. Brain research 983:128-136.
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. The Journal of neuroscience : the official journal of the Society for Neuroscience 27:10695-10702.
Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Harvey RP, Lai D, Zhou M, Brunner D, Mutel V, Gonzalo A, Lemke G, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Gurney ME, Kong A, Gulcher JR, Petursson H, Stefansson K (2002) Neuregulin 1 and susceptibility to schizophrenia. American journal of human genetics 71:877-892.
Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of general psychiatry 60:1187-1192.
Tanaka S (2006) Dopaminergic control of working memory and its relevance to schizophrenia: a circuit dynamics perspective. Neuroscience 139:153-171.
Taylor E, Rogers JW (2005) Practitioner review: early adversity and developmental disorders. Journal of child psychology and psychiatry, and allied disciplines 46:451-467.
Tzschentke TM (2001) Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Progress in neurobiology 63:241-320.
Van den Heuvel DM, Pasterkamp RJ (2008) Getting connected in the dopamine system. Progress in neurobiology 85:75-93.
van Os J, Kapur S (2009) Schizophrenia. Lancet 374:635-645.
Varty GB, Marsden CA, Higgins GA (1999) Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats. Brain research 824:197-203.
Varty GB, Paulus MP, Braff DL, Geyer MA (2000) Environmental enrichment and isolation rearing in the rat: effects on locomotor behavior and startle response plasticity. Biological psychiatry 47:864-873.
Voikar V, Polus A, Vasar E, Rauvala H (2005) Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences. Genes, brain, and behavior 4:240-252.
Vuillermot S, Weber L, Feldon J, Meyer U (2010) A longitudinal examination of the neurodevelopmental impact of prenatal immune activation in mice reveals primary defects in dopaminergic development relevant to schizophrenia. The Journal of neuroscience : the official journal of the Society for Neuroscience 30:1270-1287.
Wall VL, Fischer EK, Bland ST (2012) Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats. Physiology & behavior 107:440-450.
Wang GW, Cai JX (2008) Reversible disconnection of the hippocampal-prelimbic cortical circuit impairs spatial learning but not passive avoidance learning in rats. Neurobiology of learning and memory 90:365-373.
Wang YC, Ho UC, Ko MC, Liao CC, Lee LJ (2012) Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation. Brain structure & function 217:337-351.
Warburton EC, Brown MW (2010) Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory. Neuropsychologia 48:2262-2272.
Weiss IC, Feldon J (2001) Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology 156:305-326.
Wilkinson LS, Killcross SS, Humby T, Hall FS, Geyer MA, Robbins TW (1994) Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 10:61-72.
Xiao J, Buka SL, Cannon TD, Suzuki Y, Viscidi RP, Torrey EF, Yolken RH (2009) Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring. Microbes and infection / Institut Pasteur 11:1011-1018.
Young KA, Gobrogge KL, Wang Z (2011) The role of mesocorticolimbic dopamine in regulating interactions between drugs of abuse and social behavior. Neuroscience and biobehavioral reviews 35:498-515.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔