BRAIN and NERVE－神経研究の進歩65巻10号

2013年10月発行

特集 神経系の発達メカニズム―最近の話題

大脳皮質の神経細胞配置と統合失調症

著者： 久保健一郎¹ 仲嶋一範¹

所属機関： ¹慶應義塾大学医学部解剖学

ページ範囲：P.1133 - P.1145

文献概要

はじめに

　統合失調症の脳病理所見として，大脳皮質の微細な組織構築の異常が指摘されている。中でも，神経細胞配置の異常は，脳の発達段階において生じると考えられ，統合失調症の神経発達障害仮説に合致する所見と捉えられる。しかしその一方で，神経細胞配置の異常と統合失調症の発症の関連は明らかではない。本稿では，統合失調症の神経発達障害仮説と，正常の大脳皮質の組織構造およびその形成過程を説明したのち，統合失調症で報告された大脳皮質の微細組織構築の変化について概説する。また，それらの微細組織構築の異常がどのように生じるのか，そして統合失調症の症状にどのように結びつくのかについて考察する。

参考文献

1) Weinberger DR: From neuropathology to neurodevelopment. Lancet 346: 552-557, 1995

2) Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, et al: Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157: 16-25, 2000

3) Harrison PJ: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 122(Pt 4): 593-624, 1999

4) Arnold SE, Trojanowski JQ: Recent advances in defining the neuropathology of schizophrenia. Acta Neuropathol 92: 217-231, 1996

5) Owen MJ, O'Donovan MC, Thapar A, Craddock N: Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 198: 173, 2011

6) Fatemi SH, Folsom TD: The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 35: 528-548, 2009

7) Owen MJ, Craddock N, O'Donovan MC: Schizophrenia: genes at last? Trends Genet 21: 518-525, 2005

8) D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, et al: A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374: 719-723, 1995

9) Ogawa M, Miyata T, Nakajima K, Yagyu K, Seike M, et al: The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14: 899-912, 1995

10) Hirotsune S, Takahara T, Sasaki N, Hirose K, Yoshiki A, et al: The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons. Nat Genet 10: 77-83, 1995

11) Bar I, Lambert De Rouvroit C, Royaux I, Krizman DB, Dernoncourt C, et al: A YAC contig containing the reeler locus with preliminary characterization of candidate gene fragments. Genomics 26: 543-549, 1995

12) Kamiya A, Kubo K, Tomoda T, Takaki M, Youn R, et al: A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nat Cell Biol 7: 1167-1178, 2005

13) Kubo K, Tomita K, Uto A, Kuroda K, Seshadri S, et al: Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi. Biochem Biophys Res Commun 400: 631-637, 2010

14) Mei L, Xiong WC: Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9: 437-452, 2008

15) Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, et al: Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320: 539-543, 2008

16) Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, et al: Large recurrent microdeletions associated with schizophrenia. Nature 455: 232-236, 2008

17) Consosium International Schizophrenia: Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455: 237-241, 2008

18) Craddock N, Owen MJ: The Kraepelinian dichotomy: going, going... but still not gone. Br J Psychiatry 196: 92-95, 2010

19) Gilbert CD: Microcircuitry of the visual cortex. Annu Rev Neurosci 6: 217-247, 1983

20) Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa VH, Butt SJ, et al: Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J Neurosci 30: 1582-1594, 2010

21) Freund TF: Interneuron diversity series: rhythm and mood in perisomatic inhibition. Trends Neurosci 26: 489-495, 2003

22) Bielle F, Griveau A, Narboux-Neme N, Vigneau S, Sigrist M, et al: Multiple origins of Cajal-Retzius cells at the borders of the developing pallium. Nat Neurosci 8: 1002-1012, 2005

23) Tabata H, Yoshinaga S, Nakajima K: Cytoarchitecture of mouse and human subventricular zone in developing cerebral neocortex. Exp Brain Res 216: 161-168, 2012

24) Hansen DV, Lui JH, Parker PR, Kriegstein AR: Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464: 554-561, 2010

25) Wonders CP, Anderson SA: The origin and specification of cortical interneurons. Nat Rev Neurosci 7: 687-696, 2006

26) Gelman D, Griveau A, Dehorter N, Teissier A, Varela C, et al: A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. J Neurosci 31: 16570-16580, 2011

27) Yozu M, Tabata H, Nakajima K: Birth-date dependent alignment of GABAergic neurons occurs in a different pattern from that of non-GABAergic neurons in the developing mouse visual cortex. Neurosci Res 49: 395-403, 2004

28) Lodato S, Rouaux C, Quast KB, Jantrachotechatchawan C, Studer M, et al: Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron 69: 763-779, 2011

29) Letinic K, Zoncu R, Rakic P: Origin of GABAergic neurons in the human neocortex. Nature 417: 645-649, 2002

30) Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, et al: Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478: 382-386, 2011

31) Catts VS, Fung SJ, Long LE, Joshi D, Vercammen A, et al: Rethinking schizophrenia in the context of normal neurodevelopment. Front Cell Neurosci 7: 60, 2013

32) Uhlhaas PJ, Singer W: Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11: 100-113, 2010

33) Stephan KE, Friston KJ, Frith CD: Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 35: 509-527, 2009

34) Jakob H, Beckmann H: Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 65: 303-326, 1986

35) Kovelman JA, Scheibel AB: A neurohistological correlate of schizophrenia. Biol Psychiatry 19: 1601-1621, 1984

36) Conrad AJ, Abebe T, Austin R, Forsythe S, Scheibel AB: Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Arch Gen Psychiatry 48: 413-417, 1991

37) Jonsson SA, Luts A, Guldberg-Kjaer N, Brun A: Hippocampal pyramidal cell disarray correlates negatively to cell number: implications for the pathogenesis of schizophrenia. Eur Arch Psychiatry Clin Neurosci 247: 120-127, 1997

38) Arnold SE, Talbot K, Hahn CG: Neurodevelopment, neuroplasticity, and new genes for schizophrenia. Prog Brain Res 147: 319-345, 2005

39) Harrison PJ: The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology (Berl) 174: 151-162, 2004

40) Connor CM, Crawford BC, Akbarian S: White matter neuron alterations in schizophrenia and related disorders. Int J Dev Neurosci 29: 325-334, 2011

41) Suarez-Sola ML, Gonzalez-Delgado FJ, Pueyo-Morlans M, Medina-Bolivar OC, Hernandez-Acosta NC, et al: Neurons in the white matter of the adult human neocortex. Front Neuroanat 3: 7, 2009

42) Gertz HJ, Schmidt LG: Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome. Pharmacopsychiatry 24: 93-95, 1991

43) Akbarian S, Bunney WE Jr, Potkin SG, Wigal SB, Hagman JO, et al: Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiatry 50: 169-177, 1993

44) Akbarian S, Kim JJ, Potkin SG, Hetrick WP, Bunney WE Jr, et al: Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry 53: 425-436, 1996

45) Connor CM, Guo Y, Akbarian S: Cingulate white matter neurons in schizophrenia and bipolar disorder. Biol Psychiatry 66: 486-493, 2009

46) Simms ML, Kemper TL, Timbie CM, Bauman ML, Blatt GJ: The anterior cingulate cortex in autism: heterogeneity of qualitative and quantitative cytoarchitectonic features suggests possible subgroups. Acta Neuropathol 118: 673-684, 2009

47) Oblak AL, Rosene DL, Kemper TL, Bauman ML, Blatt GJ, et al: Altered posterior cingulate cortical cyctoarchitecture, but normal density of neurons and interneurons in the posterior cingulate cortex and fusiform gyrus in autism. Autism Res 4: 200-211, 2011

48) Morris HM, Stopczynski RE, Lewis DA: NPY mRNA expression in the prefrontal cortex: selective reduction in the superficial white matter of subjects with schizoaffective disorder. Schizophr Res 115: 261-269, 2009

49) Eastwood SL, Harrison PJ: Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry 8: 769, 821-831, 2003

50) Eastwood SL , Harrison PJ: Cellular basis of reduced cortical reelin expression in schizophrenia. Am J Psychiatry 163: 540-542, 2006

51) Ikeda K, Iritani S, Ueno H, Niizato K: Distribution of neuropeptide Y interneurons in the dorsal prefrontal cortex of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28: 379-383, 2004

52) Nopoulos P, Swayze V, Flaum M, Ehrhardt JC, Yuh WT, et al: Cavum septi pellucidi in normals and patients with schizophrenia as detected by magnetic resonance imaging. Biol Psychiatry 41: 1102-1108, 1997

53) Kiehl TR, Chow EW, Mikulis DJ, George SR, Bassett AS, et al: Neuropathologic features in adults with 22q11.2 deletion syndrome. Cereb Cortex 19: 153-164, 2009

54) Guris DL, Duester G, Papaioannou VE, Imamoto A: Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome. Dev Cell 10: 81-92, 2006

55) Sekine K, Kawauchi T, Kubo K, Honda T, Herz J, et al: Reelin controls neuronal positioning by promoting cell-matrix adhesion via inside-out activation of integrin alpha5beta1．Neuron 76: 353-369, 2012

56) Robin NH, Taylor CJ, McDonald-McGinn DM, Zackai EH, Bingham P, et al: Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation. Am J Med Genet A 140: 2416-2425, 2006

57) Wegiel J, Kuchna I, Nowicki K, Imaki H, Marchi E, et al: The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol 119: 755-770, 2010

58) Tomita K, Kubo K, Ishii K, Nakajima K: Disrupted-in-Schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development. Hum Mol Genet 20: 2834-2845, 2011

59) Kubo K, Honda T, Tomita K, Sekine K, Ishii K, et al: Ectopic Reelin induces neuronal aggregation with a normal birthdate-dependent "inside-out" alignment in the developing neocortex. J Neurosci 30: 10953-10966, 2010

60) Kostovic I, Judas M, Sedmak G: Developmental history of the subplate zone, subplate neurons and interstitial white matter neurons: relevance for schizophrenia. Int J Dev Neurosci 29: 193-205, 2011

61) Kanold PO, Shatz CJ: Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity. Neuron 51: 627-638, 2006

62) Marin O: Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 13: 107-120, 2012

63) Lewis DA, Hashimoto T, Volk DW: Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6: 312-324, 2005

64) Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM: Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31: 234-242, 2008

65) Bartos M, Vida I, Jonas P: Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci 8: 45-56, 2007

66) Kehrer C, Maziashvili N, Dugladze T, Gloveli T: Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia. Front Mol Neurosci 1: 6, 2008