Elucidation of biological basis of autism as fatty acid metabolic disease

• Project/Area Number: 21200014
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general; Metabolomics
• Research Institution: Hamamatsu University School of Medicine (2010-2011); Osaka University (2009)
• Principal Investigator: MATSUZAKI Hideo 浜松医科大学, 子どものこころの発達研究センター, 特任准教授 (00334970)
• Co-Investigator(Kenkyū-buntansha): ZAIMA Nobuhiro 近畿大学, 農学部, 講師 (40455572) ; IWATA Keiko 浜松医科大学, 子どものこころの発達研究センター, 助教 (30415088) ; OGAWA Mikako 浜松医科大学, メディカルフォトニクス研究センター, 准教授 (20344351)
• Co-Investigator(Renkei-kenkyūsha): TSUJII Masatsugu 中京大学, 現代社会学部, 教授 (20257546) ; SETOU Mitsutoshi 浜松医科大学, 医学部, 教授 (20302664) ; TSUCHIYA Kenji 浜松医科大学, 子どものこころの発達研究センター, 准教授 (20362189) ; ITOH Hiroaki 浜松医科大学, 周産母子センター, 教授 (70263085) ; MAGATA Yasuhiro 浜松医科大学, メディカルフォトニクス研究センター, 教授 (20209399)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥27,560,000 (Direct Cost: ¥21,200,000、Indirect Cost: ¥6,360,000); Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2010: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2009: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: 自閉症 / 脂質代謝異常 / 発達

Research Abstract

In this project, we were focusing on impaired Very Low Density Lipoprotein (VLDL) lipid fraction in serum of individuals with autism. Then, we examined the serum levels of fatty acid composition, autistic animal models based on the lipid profile, imaging analyze and a novel therapy method of autism by using the autistic animal model. To identify causal fatty acid of VLDL-specific lipid profile in autism, we analyzed fatty acid composition by GC-MS, which resulted in impairment of some fatty acids including omega-6. Next, we identified that CD38KO mice showed impairment of VLDL fraction and omega-6 fatty acid like autistic human subject, and found that feeding challenge of omega-6 fatty acid could rescue impairment of social recognition behavior in CD38KO mice immediately after birth. In VLDL Receptor transgenic rat (VLDLR-Tg), we examined behavior test and found that the rat showed hyperactivity and an entire impairment of arachidonic acid distribution in tissues of VLDLR-Tg.

Research Products

• [Journal Article] Triggers for Autism: genetic and environmental factors (2012)
  • Author(s): Matsuzaki H, Iwata K, Manabe T, Mori N
  • Journal Title: Journal of Central Nervous System Disease Volume: 4 Pages: 1-10
  • DOI: 10.4137/jcnsd.s9058
  • Peer Reviewed
• [Journal Article] Investigation of the serum levels of anterior pituitary hormones in male children with autism (2011)
  • Author(s): Iwata K, Matsuzaki H, Miyachi T, et al.
  • Journal Title: Mol Autism Volume: 2(1) Issue: 1 Pages: 16-16
  • DOI: 10.1186/2040-2392-2-16
  • Peer Reviewed
• [Journal Article] Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders (2011)
  • Author(s): Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shinmura C, Kawai S, Yoshihara Y, Wakuda T, Takebayashi K, Takagai S, Matsumoto K, Tsuchiya KJ, Iwata Y, Nakamura K, Tsujii M, Sugiyama S, Mori N
  • Journal Title: PLoS One Volume: 6(5) Issue: 5 Pages: e20470-e20470
  • DOI: 10.1371/journal.pone.0020470
  • Peer Reviewed
• [Journal Article] Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism (2011)
  • Author(s): Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, Iwata K, Matsumoto K, Wakuda T, Kameno Y, Suzuki K, Tsujii M, Nakamura K, Takei N, Mori N
  • Journal Title: PLoS One Volume: 6(10) Issue: 10 Pages: e25340-e25340
  • DOI: 10.1371/journal.pone.0025340
  • Peer Reviewed
• [Journal Article] Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autismSerum levels of platelet-derived growth factor BB homodimers are increased in male children with autism (2010)
  • Author(s): Kajizuka M, Miyachi T, Matsuzaki H, et al.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 34(1) Issue: 1 Pages: 154-8
  • DOI: 10.1016/j.pnpbp.2009.10.017
• [Journal Article] 子どものこころの分子生物学 (2010)
  • Author(s): 松崎秀夫
  • Journal Title: 脳21 Volume: 13(2) Pages: 26-33
• [Journal Article] Brain Serotonin and Dopamine Transporter Bindings in Adults with High-Functioning Autism. (2010)
  • Author(s): Nakamura K, Sekine Y, Ouchi Y, Tsujii M, Yoshikawa E, Futatsubashi M, Tsuchiya KJ, Sugihara G, Nishimura K, Takebayashi K, Kawai M, Iwata Y, Suzuki K, Suda S, Matsuzaki H, Yamamoto S, Matsumoto K, Sugiyama T, Takei N, Mori N.
  • Journal Title: Arch.Gen.Psychiatry. 67(1): Pages: 59-68
  • Peer Reviewed
• [Journal Article] Serum levels of platelet-derived growth factor BB homodimers are increased in male children with autism. (2010)
  • Author(s): Kajizuka M, Miyachi T, Matsuzaki H (corresponding author), Iwata K, Shinmura C, Suzuki K, Suda S, Tsuchiya KJ, Matsumoto K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. 34(1) Pages: 154-158
  • Peer Reviewed
• [Journal Article] Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferati on in rats : reversal by fluoxetine. (2010)
  • Author(s): Suzukil K, Okada K, Wakuda T, Shinmura C, Kameno Y, Iwata K, Takahashi T, Suda S, MatsuzakiH, Iwata Y, Hashimoto K, Mori N.
  • Journal Title: PLoS One 5(2)
  • Peer Reviewed
• [Journal Article] Decreased serum levels of adiponectin in subjects with autism. (2010)
  • Author(s): Kajizuka M, Miyachi T, Matsuzaki H (corresponding author), Iwata K, Shinmura C, Suzuki K, Suda S, Tsuchiya KJ, Matsumoto K, Iwata Y, Nakamura K, Tsujii M, Sugiyama T, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. 34(3) Pages: 455-458
  • Peer Reviewed
• [Journal Article] 自閉症のバイオマーカー (2009)
  • Author(s): 松崎秀夫
  • Journal Title: 脳と精神の医学 Volume: 20(4) Pages: 271-80
  • NAID: 10028262552
• [Journal Article] Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2(PCNT2) and DISC1-binding zinc finger protein (DBZ), with schizophrenia and with bipolar disorder. (2009)
  • Author(s): Anitha A, Nakamura K, Yamada K, Iwayama Y, Toyota T, Takei N, Iwata Y, Suzuki K, Sekine Y, Matsuzaki H, Kawai M, Thanseem I, Miyoshi K, Katayama T, Matsuzaki S, Baba K, Honda A, Hattori T, Shimizu S, Kumamoto N, Kikuchi M, Tohyama M, Yoshikawa T, Mori N.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet. 150B(7) Pages: 967-976
  • Peer Reviewed
• [Presentation] 自閉症スペクトラム障害の生物学的成因 (2012)
  • Author(s): 松崎秀夫
  • Organizer: 浜松子どものこころ連続講座
  • Place of Presentation: 静岡新聞ホール、浜松市
  • Year and Date: 2012-01-09
• [Presentation] 自閉症生物学的マーカー研究の展望、シンポジウム:自閉症研究の進歩 (2011)
  • Author(s): 松崎秀夫
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 京王プラザホテル、東京(新宿)
  • Year and Date: 2011-10-27
• [Presentation] 自閉症生物学的マーカー研究の展望 (2011)
  • Author(s): 松崎秀夫
  • Organizer: 第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会
  • Place of Presentation: 京王プラザホテル、東京(新宿)
  • Year and Date: 2011-10-27
• [Presentation] 自閉症スペクトラム障害のバイオマーカーを探る (2011)
  • Author(s): 松崎秀夫
  • Organizer: 財団法人明治安田こころの健康財団主催・新潟講座:そだちの臨床・トピックスと新たな成果
  • Place of Presentation: 朱鷺メッセ新潟コンベンションセンター、新潟市
  • Year and Date: 2011-10-15
• [Presentation] 自閉症スペクトラム障害のバイオマーカーを探る (2011)
  • Author(s): 松崎秀夫
  • Organizer: 明治安田こころの健康財団主催・新潟講座:そだちの臨床・トピックスと新たな成果
  • Place of Presentation: 新潟コンベンションセンター、新潟市
  • Year and Date: 2011-10-15
• [Presentation] Serum levels of anterior pituitary hormones in children with autism (2011)
  • Author(s): Matsuzaki H, Iwata K, Mori N
  • Organizer: 第54回日本神経化学会
  • Place of Presentation: Ishikawa, Japan
  • Year and Date: 2011-09-28
• [Presentation] Serum levels of anterior pituitary hormones in children with autism (2011)
  • Author(s): 松崎秀夫、岩田圭子、森則夫
  • Organizer: 第54回日本神経化学会
  • Place of Presentation: 石川県加賀市
  • Year and Date: 2011-09-28
• [Presentation] 自閉症のしくみを考える (2011)
  • Author(s): 松崎秀夫
  • Organizer: 子どものこころの発達研究講演会
  • Place of Presentation: 静岡新聞ホール、浜松市
  • Year and Date: 2011-04-02
• [Presentation] VLDL-specific hypolipidemia pattern in human subjects with autism and autistic rodent models (2011)
  • Author(s): Matsuzaki H, Iwata K, Tsuchiya KJ, et al.
  • Organizer: The 7th World Congress on Developmental Origins of Health and Disease
  • Place of Presentation: Portland, USA
• [Presentation] 自閉症児童の血清中下垂体前葉ホルモンの動態 (2011)
  • Author(s): Matsuzaki H, Iwata K, Mori N
  • Organizer: 第38回日本脳科学会
  • Place of Presentation: Naha, Japan
• [Presentation] 自閉症児童の血清中下垂体前葉ホルモンの動態 (2011)
  • Author(s): 松崎秀夫、岩田圭子、森則夫
  • Organizer: 第38回日本脳科学会
  • Place of Presentation: 沖縄県那覇市
• [Presentation] 新規バイオマーカーによる自閉症の判定方法 (2010)
  • Author(s): 松崎秀夫
  • Organizer: 六医科大学新技術説明会
  • Place of Presentation: 科学技術振興機構JSTホール、東京(市谷)
  • Year and Date: 2010-12-09
• [Presentation] 新規バイオマーカーによる自閉症の判定方法 (2010)
  • Author(s): 松崎秀夫
  • Organizer: 六医科大学新技術説明会
  • Place of Presentation: 東京(市ヶ谷)
  • Year and Date: 2010-12-09
• [Presentation] Serum adipokine levels in children with autism (2010)
  • Author(s): Matsuzaki H, Fujita-Shimizu A, Iwata K, et al.
  • Organizer: The Society for Neuroscience 40th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-16
• [Presentation] VLDLR-overexpressing transgenic rats: evaluation as an animal models of autism. (2010)
  • Author(s): Iwata K, Matsuzaki H, Izumo N, Ichitani Y, Takei N, Mori N
  • Organizer: The Society for Neuroscience 40th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-15
• [Presentation] Serum adipokine levels in children with autism. (2010)
  • Author(s): Matsuzaki H, Fujita-Shimizu A, Iwata K, Suda S, Shimmura C, Kameno Y, Mori N.
  • Organizer: The Society for Neuroscience 40th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-15
• [Presentation] Serum adipokine levels in children with autism (2010)
  • Author(s): Matsuzaki H
  • Organizer: 第53回日本神経化学会
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-09-03
• [Presentation] Serum adipokine levels in children with autism. (2010)
  • Author(s): Matsuzaki H
  • Organizer: The 53^<rd> Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-09-03
• [Presentation] VLDLR overexpression rat: evaluation as an animal model of autism. (2010)
  • Author(s): Iwata K, Matsuzaki H, Izumo N, Ichitani Y, Mori N.
  • Organizer: The 53^<rd> Annual Meeting of the Japanese Society for Neurochemistry
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-09-03
• [Presentation] Dyslipidemia in male patients with high-functioning autism (2010)
  • Author(s): Matsuzaki H, Iwata K, Suda S, et al.
  • Organizer: The 9^<th> annual International Meeting for Autism Research
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2010-05-20
• [Presentation] Dyslipidemia in male patients with high-functioning autism. (2010)
  • Author(s): Matsuzaki H, Iwata K, Suda S, Tsuchiya KJ, Suzuki K, Nakamura K, Tsujii M, Takei N, Mori N
  • Organizer: The 9＾<th> annual International Meeting for Autism Research
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2010-05-20
• [Presentation] 自閉症の判定方法および診断マーカー (2010)
  • Author(s): 松崎秀夫
  • Organizer: イノベーションジャパン
  • Place of Presentation: 科学技術振興機構、東京(有楽町)
• [Presentation] 自閉症の判定方法および診断マーカー (2010)
  • Author(s): 松崎秀夫
  • Organizer: 科学技術振興機構イノベションジャパン
  • Place of Presentation: 東京(有楽町)
• [Presentation] 高機能自閉症児に認められる特異的代謝異常の医療応用 (2009)
  • Author(s): 松崎秀夫
  • Organizer: JST(東海iネット)新技術説明会
  • Place of Presentation: 科学技術振興機構、東京
  • Year and Date: 2009-10-30
• [Presentation] 高機能自閉症児に認められる特異的代謝異常の医療応用 (2009)
  • Author(s): 松崎秀夫
  • Organizer: JST(東海iネット)新技術説明会
  • Place of Presentation: 科学技術振興機構、東京(市谷)
  • Year and Date: 2009-10-30
• [Presentation] Dyslipidemia in male patients with high-functioning autism (2009)
  • Author(s): Matsuzaki H, Iwata K, Suda S, et al.
  • Organizer: The Society for Neuroscience 39th annual meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-19
• [Presentation] Dyslipidemia in male patients with high-functioning autism. (2009)
  • Author(s): Matsuzaki H, Iwata K, Suda S, Miyachi T, Suzuki K, Nakamura K, Tsujii M, Takei N, Mori N
  • Organizer: The Society for Neuroscience 39th annual meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-19
• [Presentation] 自閉症生物学的マーカー研究の展望 (2009)
  • Author(s): 松崎秀夫
  • Organizer: 連合大学院開設記念シンポジウム「子どものこころはどこまでわかったか?」
  • Place of Presentation: 浜松市
  • Year and Date: 2009-10-03
• [Presentation] 自閉症生物学的マーカー研究の展望 (2009)
  • Author(s): 松崎秀夫
  • Organizer: 連合大学院開設記念シンポジウム
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2009-10-03
• [Presentation] A perspective of biological marker research for Autism. (2009)
  • Author(s): 松崎秀夫
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: 群馬県渋川市
  • Year and Date: 2009-06-22
• [Presentation] 浜松医科大学での自閉症メカニズム解明の試み (2009)
  • Author(s): 松崎秀夫
  • Organizer: 静岡県子どもの精神保健フォーラム
  • Place of Presentation: 浜松市
  • Year and Date: 2009-06-14
• [Presentation] 浜松医科大学での自閉症メカニズム解明の試み (2009)
  • Author(s): 松崎秀夫
  • Organizer: 静岡県子どもの精神保健フォーラム
  • Place of Presentation: 静岡県浜松市
  • Year and Date: 2009-06-14
• [Presentation] A perspective of biological marker research for Autism. (2009)
  • Author(s): 松崎秀夫
  • Organizer: 第36回日本脳科学会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2009-06-12
• [Presentation] 自閉症生物学的マーカーの展望 (2009)
  • Author(s): Matsuzaki H, Iwata K, Tsuchiya KJ, et al.
  • Organizer: 第36回日本脳科学会
  • Place of Presentation: Kanazawa, Japan
• [Presentation] A perspective of biological marker research for Autism (2009)
  • Author(s): Matsuzaki H
  • Organizer: 第52回日本神経化学会
  • Place of Presentation: Shibukawa, Japan
• [Remarks] 浜松医科大学・子どものこころの発達研究センター ホームページ
  • URL: http://www.rccmd.org/
• [Patent(Industrial Property Rights)] 高機能自閉症の発症危険度を判定する方法およびマーカー (2010)
  • Inventor(s): 森則夫、中村和彦、鈴木勝昭、土屋賢治、岩田圭子、松崎秀夫
  • Industrial Property Rights Holder: 国立大学法人浜松医科大学
  • Filing Date: 2010-10-14
  • Overseas
• [Patent(Industrial Property Rights)] 高機能自閉症の発症危険度を判定する方法およびマーカー (2010)
  • Inventor(s): 森則夫、中村和彦、鈴木勝昭、土屋賢治、岩田圭子、松崎秀夫
  • Industrial Property Rights Holder: 国立大学法人浜松医科大学
  • Industrial Property Number: 2011-536046
  • Filing Date: 2010-10-14
• [Patent(Industrial Property Rights)] 高機能自閉症の発症危険度を判定する方法およびマーカー (2010)
  • Inventor(s): 森則夫、中村和彦、鈴木勝昭、土屋賢治、岩田圭子、松崎秀夫
  • Industrial Property Rights Holder: 国立大学,法人浜松,医科大学
  • Filing Date: 2010-10-14
  • Overseas
• [Patent(Industrial Property Rights)] 高機能自閉症の発症危険度を判定する方法およびマーカー (2009)
  • Inventor(s): 森則夫、中村和彦、鈴木勝昭、土屋賢治、岩田圭子、松崎秀夫
  • Industrial Property Rights Holder: 国立大学法人浜松医科大学
  • Industrial Property Number: 2009-236976
  • Filing Date: 2009-10-14