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Brain hyperserotonemia causes autism-relevant social deficits in mice
http://hdl.handle.net/10191/51320
http://hdl.handle.net/10191/51320d7ed8472-ac65-47f9-abf5-8d484f79085b
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2019-07-09 | |||||
| タイトル | ||||||
| タイトル | Brain hyperserotonemia causes autism-relevant social deficits in mice | |||||
| タイトル | ||||||
| タイトル | Brain hyperserotonemia causes autism-relevant social deficits in mice | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 脳のセロトニン過剰はマウスで自閉症関連の社会的障害を引き起こす | |||||
| 著者 |
Tanaka, Miho
× Tanaka, Miho |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 175130 | |||||
| 姓名 | 田中, 美歩 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: Hyperserotonemia in the brain is suspected to be an endophenotype of autism spectrum disorder(ASD). Reducing serotonin levels in the brain through modulation of serotonin transporter function may improve ASD symptoms. Methods: We analyzed behavior and gene expression to unveil the causal mechanism of ASD-relevant social deficits using serotonin transporter (Sert) knockout mice. Results: Social deficits were observed in both heterozygous knockout mice (HZ) and homozygous knockout mice (KO), but increases in general anxiety were only observed in KO mice. Two weeks of dietary restriction of the serotonin precursor tryptophan ameliorated both brain hyperserotonemia and ASD-relevant social deficits in Sert HZ and KO mice. The expression of rather distinct sets of genes was altered in Sert HZ and KO mice, and a substantial portion of these genes was also affected by tryptophan depletion. Tryptophan depletion in Sert HZ and KO mice was associated with alterations in the expression of genes involved in signal transduction pathways initiated by changes in extracellular serotonin or melatonin, a derivative of serotonin. Only expression of the AU015836 gene was altered in both Sert HZ and KO mice. AU015836 expression and ASD-relevant social deficits normalized after dietary tryptophan restriction. Conclusions: These findings reveal a Sert gene dose-dependent effect on brain hyperserotonemia and related behavioral sequelae in ASD and a possible therapeutic target to normalize brain hyperserotonemia and ASD-relevant social deficits. Keywords: Serotonin transporter, Tryptophan depletion, Autism spectrum disorder, Heterozygous mice |
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| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 学位の種類: 博士（医学）. 報告番号: 甲第4520号. 学位記番号: 新大院博（医）甲第842号. 学位授与年月日: 平成31年3月25日 | |||||
| 書誌情報 | 発行日 2019-03-25 | |||||
| 出版者 | ||||||
| 出版者 | 新潟大学 | |||||
| 権利 | ||||||
| 権利情報 | 【○!C】The Author(s). 2018 | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-25 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4520号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博（医）甲第842号 | |||||
