Involvement of social interaction deficits and histone modification in brain

• Project/Area Number: 22791013
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MIZUMA Hiroshi 独立行政法人理化学研究所, 分子プローブ機能評価研究チーム, 研究員 (00382200)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: PET / ヒストン脱アセチル化 / 小児自閉症 / 社会的相互作用 / ラット / 社会相互作用 / ヒストン修飾

Research Abstract

Social interaction deficits are one of the major characteristics in autism. To investigate the relationship between social interaction deficits and histone modification in brain, we measured the developmental changes in histone deacetylation in the rat brain by positron emission tomography (PET) imaging using with 6-([^<18>F]-fluoroacetamide)-1-hexanoicanilide ([^<18>F]FAHA). A gradual increase in brain uptake of [18F]FAHA was observed from infantile to adult period in parallel with acquisition of social interaction skills. The regional uptake of [^<18>F]FAHA showed higher uptake in the cerebral cortex and striatum than that in other brain regions. These results indicate that [18F]FAHA-PET imaging could be visualize in vivo histone deacetylation and might be helpful for monitoring HDAC activity in human study.

Research Products

• [Journal Article] Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with (18)F-FAHA (2013)
  • Author(s): Yeh HH et al.
  • Journal Title: Neuroimage Volume: 64 Pages: 630-639
  • DOI: 10.1016/j.neuroimage.2012.09.019
  • Peer Reviewed
• [Journal Article] Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with (18)F-FAHA
  • Author(s): Yeh HH, Tian M, Hinz R, Young D, Shavrin A, Mukhapadhyay U, Flores LG, Balatoni J, Soghomonyan S, Jeong HJ, Pal A, Uthamanthil R, Jackson JN, Nishii R, Mizuma H, Onoe H, Kagawa S, Higashi T, Fukumitsu N, Alauddin M, Tong W, Herholz K, Gelovani JG.
  • Journal Title: NeuroImage Volume: 64(1) Pages: 630-639
  • Peer Reviewed
• [Presentation] 脳内ヒストン脱アセチル化酵素活性の発達に伴う変化:[^<18>F]FAHAを用いた検討 (2011)
  • Author(s): 水間広, 西井龍一, 加川信也, 立花晃子, 大野正裕, 平尾有日子, 高橋和弘, 東達也, Juri G Gelovani, 尾上浩隆
  • Organizer: 第6回日本分子イメージング学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-05-26
• [Presentation] 脳内ヒストン脱アセチル化酵素活性の脳神経活動に伴う変化:[^<18>F]FAHAを用いた検討 (2011)
  • Author(s): 西井龍一, 水間広, 加川信也, 立花晃子, 大野正裕, 平尾有日子, 高橋和弘, 東達也, 長町茂樹, 川井恵一, 田村正三, Juri G Gerovani, 尾上浩隆
  • Organizer: 第6回日本分子イメージング学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-05-26
• [Presentation] Activity-related changes in brain HDAC with [F-18]FAHA PET in rats and monkeys (2011)
  • Author(s): Nishii R, Mizuma H, Kagawa S, Yamanaka H, Tachibana A, Takahashi K, Higashi T, Gelovani JG, Onoe H
  • Organizer: SNM2011, 58th Annual Meeting of Society of Neclear Medicine
  • Place of Presentation: San Antonio, TX, USA
• [Presentation] 脳内ヒストン脱アセチル化酵素活性の脳神経活動に伴う変化 : [18F]FAHA を用いた検討 (2011)
  • Author(s): 西井龍一,水間広,加川信也,立花晃子,大野正裕,平尾有日子,高橋和弘,東達也,長町茂樹,川井恵一,田村正三,Juri G Gerovani,尾上浩隆
  • Organizer: 第6回日本分子イメージング学会
  • Place of Presentation: 神戸
• [Presentation] 脳内ヒストン脱アセチル化酵素活性の発達に伴う変化:[^<18>F]FAHA を用いた検討 (2011)
  • Author(s): 水間広,西井龍一,加川信也,立花晃子,大野正裕,平尾有日子,高橋和弘,東達也,Juri G Gelovani,尾上浩隆
  • Organizer: 第6回日本分子イメージング学会
  • Place of Presentation: 神戸
• [Presentation] Activity-related Changes in Brain HDAC using [^<18>F]FAHA PET in Rats and Monkeys. (2010)
  • Author(s): Nishii R, Mizuma H, Kagawa S, Tachibana A, Takahashi K, Yamanaka H, Higashi T, Gelovani JG, Onoe H
  • Organizer: World Molecular Imaging Congress 2010
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-09-09
• [Presentation] Developmental changes in brain HDAC activity in rodents and non-human primates measured by [^<18>F]FAHA-PET. (2010)
  • Author(s): Mizuma H, Nishii R, Kagawa S, Tachibana A, Takahashi K, Tamura Y, Higashi T, Gelovani JG, Onoe H
  • Organizer: SNM2010, 57th Annual Meeting of Society of Neclear Medicine
  • Place of Presentation: Salt Lake City, UT, USA
  • Year and Date: 2010-06-08
• [Presentation] Activity-related Changes in Brain HDAC using [18F]FAHA PET in Rats and Monkeys (2010)
  • Author(s): Nishii R, Mizuma H, Kagawa S, Tachibana A, Takahashi K, Yamanaka H, Higashi T, Gelovani JG, Onoe H
  • Organizer: World Molecular Imaging Congress 2010
  • Place of Presentation: Kyoto, Japan
• [Presentation] Developmental changes in brain HDAC activity in rodents and non-human primates measured by [^<18>F]FAHA-PET (2010)
  • Author(s): Mizuma H, Nishii R, Kagawa S, Tachibana A, Takahashi K, Tamura Y, Higashi T, Gelovani JG, Onoe H
  • Organizer: SNM2010, 57th Annual Meeting of Society of Neclear Medicine
  • Place of Presentation: Salt Lake City, UT, USA
• [Remarks] SNM Poster Award Neurosciences Track Second Place. Developmental changes in brain HDAC activity in rodents and non-human primates measured by [18F]FAHA-PET. 57th Annual Meeting of Society of Neclear Medicine. Jun. 5th-9th, 2010. [受賞]
  • URL: http://www.cmis.riken.jp/news/2010/1006mizuma.html