Multiple analysis of intracellular responases in intractable disease related to dopaminergic neuron vulnerability with the use of Parkinson's Disease specific iPS cells

• Project/Area Number: 25830055
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hoshi University (2014); Keio University (2013)
• Principal Investigator: KUZUMAKI Naoko 星薬科大学, 薬学部, 講師 (10507669)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: iPS 細胞 / パーキンソン病 / メタボローム / ドパミン神経 / メタボローム解析 / 疾患特異的iPS 細胞

Outline of Final Research Achievements

In the present study, iPSCs were generated from two Parkinson’s patients and two control subjects. All of the clones differentiated into neurons included tyrosine hydroxylase-positive neurons. Under the present condition, I found differences in gene expression between control and patients. Among those, the expression level of PGC-1α, which plays a key role in mitochondrial biogenesis and energy metabolism, in Parkinson’s specific-iPS cell (PD-iPSCs)-derived dopaminergic (DA) neurons was significantly lower than that in control. Using CE-MS-system, I found the change in the expression of several metabolites in glycolysis and glutathione metabolism pathways in DA neuron-derived from PD-iPSCs. Interestingly, the expression of S-adenosylmethionone, which can lead to methylation of DNA, was significantly increased in PD-iPSCs-derived DA neurons. These findings suggest that metabolic abnormality in DA neurons could lead to neuronal dysfunction in PD.

Research Products

• [Journal Article] Changes in circadian rhythm for mRNA expression of melatonin 1A and 1B receptors in the hypothalamus under a neuropathic pain-like state. (2014)
  • Author(s): Odo M, Koh K, Takada T, Yamashita A, Narita M, Kuzumaki N, Ikegami D, Sakai H, Iseki M, Inada E, Narita M.
  • Journal Title: Synapse Volume: 68 Issue: 4 Pages: 153-158
  • DOI: 10.1002/syn.21728
  • Peer Reviewed / Open Access
• [Journal Article] Astrocytic activation in the anterior cingulate cortex is critical for sleep disorder under neuropathic pain. (2014)
  • Author(s): Yamashita A, Hamada A, Suhara Y, Kawabe R, Yanase M, Kuzumaki N, Narita M, Matsui R, Okano H, Narita M.
  • Journal Title: Synapse Volume: 68 Issue: 6 Pages: 235-247
  • DOI: 10.1002/syn.21733
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain. (2013)
  • Author(s): Imai S, Ikegami D, Yamashita A, Shimizu T, Narita M, Niikura K, Furuya M, Kobayashi Y, Miyashita K, Okutsu D, Kato A, Nakamura A, Araki A, Omi K, Nakamura M, James Okano H, Okano H, Ando T, Takeshima H, Ushijima T, Kuzumaki N, Suzuki T, Narita M.
  • Journal Title: Brain Volume: 136 Issue: 3 Pages: 828-843
  • DOI: 10.1093/brain/aws330
  • Peer Reviewed
• [Journal Article] Kappa-Opioids inhibit tumor angiogenesis by suppressing VEGF signaling. (2013)
  • Author(s): Yamamizu K, Furuta S, Hamada Y, Yamashita A, Kuzumaki N, Narita M, Doi K, Katayama S, Nagase H, Yamashita JK, Narita M.
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 3213-3213
  • DOI: 10.1038/srep03213
  • Peer Reviewed / Open Access
• [Presentation] ヒト疾患特異的 iPS 細胞技術を用いたドパミン神経依存性難治疾患における 細胞内応答の多角的解析 (2015)
  • Author(s): 葛巻直子
  • Organizer: 第 88 回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
  • Invited
• [Presentation] Parkinson 病患者由来iPS細胞から分化誘導した神経細胞にみられる特異的な細胞エネルギー代謝異常とドパミン代謝変動 (2014)
  • Author(s): 須田雪明
  • Organizer: 第44 回日本神経精神薬理学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] Changes in dopamine receptor expression in iPSC-derived neurons of patients with familial Parkinson’s disease (2014)
  • Author(s): 葛巻直子
  • Organizer: 第37 回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] 多能性幹細胞の分化指向性におけるオピオイドの役割 (2014)
  • Author(s): 葛巻直子
  • Organizer: 第87 回日本薬理学会年会
  • Place of Presentation: 仙台国際センター
• [Presentation] Analyses of oxidative stress and metabolic dynamics in PARK2 iPSC-derived neurons (2013)
  • Author(s): 葛巻直子
  • Organizer: Inter national society for stem cell research 11th annual meeting
  • Place of Presentation: Boston Convention and Exhibition Center, Boston, MA, U.S.A
• [Presentation] Role of opioid system in the cell differentiation from pluripotent stem cells (2013)
  • Author(s): 葛巻直子
  • Organizer: International Narcotics Research Conference 2013 meeting
  • Place of Presentation: Pullman Cairns International Hotel, North Queensland, Australia
• [Presentation] パーキンソン病患者 iPS 細胞由来神経細胞における酸化ストレス応答ならびに代謝動態の解析 (2013)
  • Author(s): 葛巻直子
  • Organizer: Neuro 2013
  • Place of Presentation: 国立京都国際会館・京都
• [Presentation] Analyses of metabolic dynamics in iPSC-derived neurons from patient with familial Parkinson’s disease (2013)
  • Author(s): 葛巻直子
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, CA, USA
• [Book] がん疼痛緩和ケア (2014)
  • Author(s): 葛巻直子
  • Total Pages: 6
  • Publisher: じほう