Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia

被引：221

作者：

Bundo, Miki ^{[1
,2
]}

Toyoshima, Manabu ^{[3
]}

Okada, Yohei ^{[4
]}

Akamatsu, Wado ^{[4
]}

Ueda, Junko ^{[2
]}

Nemoto-Miyauchi, Taeko ^{[2
]}

Sunaga, Fumiko ^{[1
]}

Toritsuka, Michihiro ^{[5
]}

Ikawa, Daisuke ^{[5
]}

Kakita, Akiyoshi ^{[6
]}

Kato, Motoichiro ^{[7
]}

Kasai, Kiyoto ^{[8
]}

Kishimoto, Toshifumi ^{[5
]}

Nawa, Hiroyuki ^{[9
]}

Okano, Hideyuki ^{[4
]}

Yoshikawa, Takeo ^{[3
]}

Kato, Tadafumi ^{[2
]}

Iwamoto, Kazuya ^{[1
,10
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Mol Psychiat, Tokyo 1138655, Japan

[2] RIKEN, Brain Sci Inst, Lab Mol Dynam Mental Disorders, Saitama 3510198, Japan

[3] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Saitama 3510198, Japan

[4] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan

[5] Nara Med Univ, Dept Psychiat, Nara 6348521, Japan

[6] Niigata Univ, Brain Res Inst, Dept Pathol, Niigata 9518585, Japan

[7] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo 1608582, Japan

[8] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138655, Japan

[9] Niigata Univ, Brain Res Inst, Dept Mol Neurobiol, Niigata 9518585, Japan

[10] Japan Sci & Technol Agcy, PRESTO, Saitama 3320012, Japan

来源：

NEURON | 2014年 / 81卷 / 02期

关键词：

PRENATAL IMMUNE ACTIVATION; HUMAN BRAIN; POSTMORTEM BRAINS; BIPOLAR DISORDER; STEM-CELLS; EXPRESSION; 22Q11.2; MICRODELETIONS; DYSFUNCTION; ANEUPLOIDY;

D O I：

10.1016/j.neuron.2013.10.053

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. However, whether aberrant L1 retrotransposition occurs in mental disorders is unknown. Here, we report high L1 copy number in schizophrenia. Increased L1 was demonstrated in neurons from prefrontal cortex of patients and in induced pluripotent stem (iPS) cell-derived neurons containing 22q11 deletions. Whole-genome sequencing revealed brain-specific L1 insertion in patients localized preferentially to synapse- and schizophrenia-related genes. To study the mechanism of L1 transposition, we examined perinatal environmental risk factors for schizophrenia in animal models and observed an increased L1 copy number after immune activation by poly-I:C or epidermal growth factor. These findings suggest that hyperactive retrotransposition of L1 in neurons triggered by environmental and/or genetic risk factors may contribute to the susceptibility and pathophysiology of schizophrenia.

引用

页码：306 / 313

页数：8

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