New strategy for treatment of spinal cord injury by neuropeptide

• Project/Area Number: 15K15670
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Hoshi University
• Principal Investigator: Shioda Seiji 星薬科大学, 先端生命科学研究所, 教授 (80102375)
• Co-Investigator(Kenkyū-buntansha): 土肥 謙二 昭和大学, 医学部, 教授 (20301509) ; 中町 智哉 富山大学, 大学院理工学研究部(理学), 助教 (30433840)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: PACAP / 脊髄損傷 / 神経細胞死防御 / 神経再生

Outline of Final Research Achievements

PACAP (Pituitary Adenylate Cyclase-Activating Polyeptide) is a neuropeptide having neuronal protection, nerve repair and neuroregeneration activity. We have found that in the experiment using a spinal cord injury model of mouse, PACAP suppresses nerve cell death with a very low concentration. Furthermore, functional analysis of neuronal cell death inhibition by PACAP was performed, and it was also revealed that PACAP promotes axon outgrowth by promoting the expression of CRMP2 (Collapsin response mediator protein, axon elongation protein) in nerve cells. These findings suggest that PACAP promotes recovery of motor function by inducing axon regeneration after injury in nerve cell injured region in the spinal cord. PACAP may be used as a remedy for spinal cord injury in near future.

Research Products

• [Journal Article] Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion. (2017)
  • Author(s): Sasaki S, Watanabe J, Ohtaki H, Matsumoto M, Murai N, Nakamachi T, Hannibal J, Fahrenkrug J, Hashimoto H, Watanabe H, Sueki H, Honda K, Miyazaki A, Shioda S.
  • Journal Title: Br J Dermatol. Volume: 176 Issue: 2 Pages: 413-422
  • DOI: 10.1111/bjd.14885
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of the autonomic nervous system in the tumor- micro-environment and its therapeutic potential. (2016)
  • Author(s): XU Z, SHIODA S, JINUSHI M, KAWAKAMI Y, OHTAKI H, WANG S, ZHAO X, LIU Y, ZHOU D, GUO Y.
  • Journal Title: Curr Pharm Des. Volume: 23 Issue: 11 Pages: 1687-1692
  • DOI: 10.2174/1381612822666161025152942
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bihavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8. (2016)
  • Author(s): WADA N, YAMANAKA S, SHIOBATO J, RAKWAL R, HIRAKO S, IIZUKA Y, KIM H, MATSUMOTO A, KIMURA A, TAKENOYA F, YASUNAGA G, SHIODA S
  • Journal Title: Genom Data Volume: 10 Pages: 38-50
  • Peer Reviewed
• [Journal Article] PACAP suppresses dry eye signs by stimulating tear secretion (2016)
  • Author(s): Nakamachi T, Ohtaki H, Seki T, Yofu S, Kagami N, Hashimoto H, Shintani N, Baba A, Mark L, Lanekoff I, Kiss P, Farkas J, Reglodi D, Shioda S.
  • Journal Title: Nat. Commun. Volume: 7 Issue: 1 Pages: 12034-12034
  • DOI: 10.1038/ncomms12034
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide enhances saliva secretion via direct binding to PACAP receptors of major salivary glands in mice. (2016)
  • Author(s): MATOBA Y, NONAKA N, TAKAGI Y, IMAMURA E, NARUKAWA M, NAKAMACHI T, SHIODA S, BANKS WA, NAKAMURA M
  • Journal Title: Anat Rec (Hoboken) Volume: 299 Issue: 9 Pages: 1293-1299
  • DOI: 10.1002/ar.23388
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Unlabeling the rat blood genome-wide transcriptome after oral administration of lavender oil by a two-color dye-swap DNA microarray approach. (2016)
  • Author(s): HORI M, KUBO H, SHIBATO J, SAITO T, OGAWA T, WAKAMORI M, MASUO Y, SHIODA S, RAKWAL R
  • Journal Title: Genom Data Volume: 8 Pages: 139-145
  • DOI: 10.1016/j.gdata.2016.05.005
  • Peer Reviewed / Open Access
• [Journal Article] Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice. (2016)
  • Author(s): KAGEYAMA H, SHIBA K, HIRAKO S, WADA N, YAMANAKA S, NOGI Y, TAKENOYA F, NONAKA N, HIRAKO S, INOUE S, SHIODA S
  • Journal Title: Sci Rep. Volume: 6 Pages: 28200-28200
  • Peer Reviewed / Open Access
• [Journal Article] Fish oil and fenofibrate inhibit pancreatic islet hypertrophy, and improve glucose and lipid metabolic dysfuntions with different ways in diabetic KK mice. (2016)
  • Author(s): Nakasatomi M, Kim H, Arai T, Hirako S, Shioda S, Iizuka Y, Sakurai K, Matsumoto A
  • Journal Title: Obes Res Clin Pract Volume: Epub ahead of print Issue: 1 Pages: 29-38
  • DOI: 10.1016/j.orcp.2016.03.012
  • NAID: 120006470025
  • Peer Reviewed
• [Journal Article] Narcolepsy-like sleep disturbance in orexin kcnokout mice are normalized by the 5-HT1A receptor agonist 8-OH-DPAT. (2016)
  • Author(s): MORI T, UZAWA N, IWASE Y, MASUKAWA D, RAHMADI M, HIRAYAMA S, HOKAZONO M, HIGASHIYAMA K, SHIODA S, SUZUKI T
  • Journal Title: Psychopharmacology (Berl). Volume: 233 Issue: 12 Pages: 2343-2353
  • DOI: 10.1007/s00213-016-4282-1
  • Peer Reviewed
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor. (2016)
  • Author(s): Xu Z, Ohtaki H, Watanabe J, Miyamoto K, Murai N, Sasaki S, Matsumoto M, Hashimoto H, Hiraizumi Y, Numazawa S, Shioda S.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 22373-22373
  • DOI: 10.1038/srep22373
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in adult mouse hippocampal neurogenesis after stroke. (2016)
  • Author(s): Matsumoto M, Nakamachi T, Watanabe J, Sugiyama K, Ohtaki H, Murai N, Sasaki S, Xu Z, Hashimoto H, Seki T, Miyazaki A, Shioda S.
  • Journal Title: J Mol Neurosci Volume: 10 Issue: 2 Pages: 1007-1007
  • DOI: 10.1007/s12031-016-0731-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue. (2016)
  • Author(s): HirakoS, Wada N, Kageyama H, Takenoya F , Izumida Y, Kim H, IizukaY, Matsumoto A, Okabe M, Kimura A, Suzuki M, Yamanaka S, Shioda S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 1-9
  • DOI: 10.1038/srep21481
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons. (2016)
  • Author(s): Ardianto C, Yonemochi N, Yamamoto S, Yang L, Takenoya F, Shioda S, Nagase H, Ikeda H, Kamei J.
  • Journal Title: Neuroscience. Volume: 320 Pages: 183-193
  • DOI: 10.1016/j.neuroscience.2016.02.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hepatic lipid accumulation is ameliorated in obese KK mice by dietary sei whale oil. (2016)
  • Author(s): Hirako S, Suzuki M, Kim H, Iizuka I, Matsumoto A, Wada N, Okabe M, Takenoya F, Yasunaga G, Yamanaka S, Miyazaki A, Shioda S.
  • Journal Title: Fish Sci. Volume: 82 Issue: 3 Pages: 509-517
  • DOI: 10.1007/s12562-016-0971-2
  • NAID: 40020863321
  • Peer Reviewed
• [Journal Article] Pleiotropic and retinoprotective functions of PACAP. (2016)
  • Author(s): SHIODA S, TAKENOYA F, WADA N, HIRABAYASHI T, SEKI T, NAKAMACHI T
  • Journal Title: Anat Sci Int. Volume: 91 Issue: 4 Pages: 313-324
  • DOI: 10.1007/s12565-016-0351-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autonomic nervous system-mediated effects of GALP on energy metabolism (2016)
  • Author(s): HIRAKO S, WADA N, KAGEYAMA H, TAKENOYA F, INOUE S, SHIODA S
  • Journal Title: Folia Pharmacologica Japonica Volume: 148 Issue: 1 Pages: 23-27
  • DOI: 10.1254/fpj.148.23
  • NAID: 130005164793
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between aquaglyceroporin expression and development of fatty liver in diet-induced obesity and ob/ob mice. (2015)
  • Author(s): Hirako S, Wakayama Y, Kim H, Iizuka Y, Matsumoto A, Wada N, Kimura A, Okabe M, Sakagami J, Suzuki M, Takenoya F, Shioda S
  • Journal Title: Obes Res Clin Pract Volume: Epub ahead of print Issue: 6 Pages: 38-50
  • DOI: 10.1016/j.orcp.2015.12.001
  • Peer Reviewed / Open Access
• [Journal Article] 2D-DIGE-based proteome expression changes in leaves of rice seedlings exposed to low-level gamma radiation at Iitate village, Fukushima. (2015)
  • Author(s): Hayashi G, Moro CF, Rohila JS, Shibato J, Kubo A, Imanaka T, Kimura S, Ozawa S, Fukutani S, Endo S, Ichikawa K, Agrawal GK, Shioda S, Hori M, Fukumoto M, Rakwal R
  • Journal Title: Plant Signal Behav Volume: 10 Issue: 12 Pages: e1103406-e1103406
  • DOI: 10.1080/15592324.2015.1103406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP). (2015)
  • Author(s): Tsumuraya T, Ohtaki H, Song D, Sato A, Watanabe J, Hiraizumi Y, Nakamachi T, Xu Z, Dohi K, Hashimoto H, Atsumi T, Shioda S.
  • Journal Title: J Neuroinflammation. Volume: 12(1) Issue: 1 Pages: 35-35
  • DOI: 10.1186/s12974-015-0252-5
  • Peer Reviewed / Open Access
• [Journal Article] Ghrelin suppresses proliferation of fetal neural progenitor cells, and induces their differentiation into neurons. (2015)
  • Author(s): Watanabe J, Matsumoto M, Kageyama H, Murai N, Sasaki S, Hirako S, Wada N, Arata S, Shioda S
  • Journal Title: Peptides Volume: 69 Pages: 40-46
  • DOI: 10.1016/j.peptides.2015.03.014
  • Peer Reviewed
• [Journal Article] Unraveling the seed endosperm proteome of the lotus (Nelumbo nucifera Gaertn.) utilizing 1DE and 2DE separation in conjunction with tandem mass spectrometry. (2015)
  • Author(s): Moro CF, Fukao Y, Shibato J, Rakwal, Timperio AM, Zolla L, Agrawal GK, Shioda S, Kouzuma Y, Yonekura M
  • Journal Title: Proteomics Volume: 15 Issue: 10 Pages: 1717-1735
  • DOI: 10.1002/pmic.201400406
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders. (2015)
  • Author(s): Muneoka K, Kuwagata M, Ogawa T, Shioda S.
  • Journal Title: Cerebellum. Volume: 14(2) Issue: 2 Pages: 86-96
  • DOI: 10.1007/s12311-014-0611-2
  • Peer Reviewed
• [Presentation] Intranasal administration of GALP suppressed the lipid accumulation in the liver. (2016)
  • Author(s): Hirako S, Kageyama H, Takaenoya F, Wada N, Okabe M, Shioda S.
  • Organizer: 13th International Congress on Obesity
  • Place of Presentation: バンクーバー、カナダ
  • Year and Date: 2016-05-01
• [Presentation] マウスにおけるPACAPの唾液分泌促進作用 (2016)
  • Author(s): 中町智哉, 渡邊 潤, 塩田清二
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2016-03-28
• [Presentation] 神経ペプチドPACAPの多彩な生理作用 (2016)
  • Author(s): 塩田清二
  • Organizer: 第13回GPCR研究会
  • Place of Presentation: 日本科学未来館（東京）
  • Invited
• [Presentation] エクリン汗腺におけるPACAPの汗分泌促進作用 (2016)
  • Author(s): 渡邊 潤、佐々木 駿、中町智哉、大滝博和、荒田 悟、本田一穂、塩田清二
  • Organizer: 第13回GPCR研究会
  • Place of Presentation: 日本科学未来館（東京）
• [Presentation] PACAPはアクアポリン5を介して涙液分泌を促進する (2016)
  • Author(s): 中町 智哉、大滝博和、関 保、渡邊 潤、塩田 清二
  • Organizer: 第13回GPCR研究会
  • Place of Presentation: 日本科学未来館（東京）
• [Presentation] Neuroprotective and neurogenic effect of PACAP after stroke (2016)
  • Author(s): Nakamachi T, Shioda S
  • Organizer: Satellite Symposium of REGPEP2016
  • Place of Presentation: Rouen, France
  • Int'l Joint Research / Invited
• [Presentation] Neuroprotective effect of PACAP on spinal cord injury through CRMP-2 protein (2016)
  • Author(s): Shioda S
  • Organizer: REGPEP2016
  • Place of Presentation: Rouen, France
  • Int'l Joint Research / Invited
• [Presentation] Impairment of memory and learning and hippocampal oxidative damage in aged PACAP deficient mouse. (2015)
  • Author(s): Nakamachi, T., Matsuda, K., and Shioda, S.,
  • Organizer: CompBiol 2015
  • Place of Presentation: 広島
  • Year and Date: 2015-12-11
  • Int'l Joint Research
• [Presentation] Effects of PACAP on the secretions of tear and saliva in mouse. (2015)
  • Author(s): Nakamachi, T., Watanabe, J., Seki, T., Ohtaki, H., and Shioda, S.,
  • Organizer: Neuropeptide 2015
  • Place of Presentation: アバディーン、イギリス
  • Year and Date: 2015-09-28
  • Int'l Joint Research
• [Presentation] Crucial role of PACAP in neural progenitor cells during development and after degeneration. (2015)
  • Author(s): Watanabe, J., Ohtaki, H., Nakamachi, T., Matsumoto, M., Sasaki, S., Murai, N., Arata, S., and Shioda, S.
  • Organizer: Neuropeptide 2015
  • Place of Presentation: アバディーン、イギリス
  • Year and Date: 2015-09-28
  • Int'l Joint Research
• [Presentation] PACAP attenuates retinal damage in association with modulation of the microglia/macrophage status and cytokines expression. (2015)
  • Author(s): Nakamachi, T., Wada, Y., Endo, K., Seki, T., and Shioda, S.
  • Organizer: 12th international symposium on VIP/PACAP and related peptides
  • Place of Presentation: カッパドキア、トルコ
  • Year and Date: 2015-09-21
  • Int'l Joint Research
• [Presentation] Neuroprotective effect of PACAP on spinal cord injury through CRMP2 protein. (2015)
  • Author(s): Shioda, S., Takenoya, F., Hori, M., Shibato, J., Nakamachi, T., and Rakwal, R
  • Organizer: 12th international symposium on VIP/PACAP and related peptides
  • Place of Presentation: カッパドキア、トルコ
  • Year and Date: 2015-09-21
  • Int'l Joint Research
• [Presentation] Involvement of PACAP in differentiation of neural progenitor cells via radial glia. (2015)
  • Author(s): Watanabe, J., Ohtaki, H., Nakamachi, T., Sasaki, S., Matsumoto, M., Murai, N., Seki, T., Arata, S., and Shioda, S.
  • Organizer: 12th international symposium on VIP/PACAP and related peptides,
  • Place of Presentation: カッパドキア、トルコ
  • Year and Date: 2015-09-21
  • Int'l Joint Research
• [Presentation] PACAP contributes proliferation of hippocampal neural stem/progenitor cells after global ischemia in mice. (2015)
  • Author(s): Nakamachi, T., Ohtaki, H., Watanabe, J., and Shioda, S.
  • Organizer: 12th international symposium on VIP/PACAP and related peptides
  • Place of Presentation: カッパドキア、トルコ
  • Year and Date: 2015-09-21
  • Int'l Joint Research
• [Presentation] PACAP 遺伝子欠損マウスにおける加齢に伴う学習記憶障害 (2015)
  • Author(s): 中町智哉, 松田恒平, 塩田清二，
  • Organizer: 日本動物学会第86回大会
  • Place of Presentation: 新潟
  • Year and Date: 2015-09-17
• [Presentation] GALPによる自律神経系を介した脂質代謝調節機構 (2015)
  • Author(s): 平子哲史、竹ノ谷文子、和田亘弘、塩田清二
  • Organizer: 第12回GPCR研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-15
• [Presentation] PACAPの唾液および汗分泌促進作用 (2015)
  • Author(s): 中町智哉、渡邊 潤、佐々木駿、塩田清二
  • Organizer: 第12回GPCR研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-15
• [Presentation] Effect of intranasal GALP on obesity and hepatic lipid metabolism in obese mice. (2015)
  • Author(s): Hirako S, Kageyama H, Takaenoya F, Wada N, Okabe M, Shioda S
  • Organizer: 12th Asian Congress of Nutrition.
  • Place of Presentation: 横浜
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Book] Pituitary Adenylate Cyclase Activating Polypeptide- Current Topics in Neurotoxicity 11. (2016)
  • Author(s): WATANABE J, SEKI T, SHIODA S
  • Total Pages: 840
  • Publisher: Springer
• [Book] Pituitary Adenylate Cyclase Activating Polypeptide- Current Topics in Neurotoxicity 11. (2016)
  • Author(s): OHTAKI H, SHIODA S
  • Total Pages: 840
  • Publisher: Springer
• [Book] 特集 未病・健康ー病気にならないための衣・食・住そしてココロ (2016)
  • Author(s): 塩田清二、竹ノ谷文子、亀井淳三 他
  • Total Pages: 83
  • Publisher: Biophilia
• [Book] アンチエイジング医学の基礎と臨床 (2015)
  • Author(s): 藤英胤（編集）、塩田清二、竹ノ谷文子 他
  • Total Pages: 447
  • Publisher: メジカルビュー社
• [Patent(Industrial Property Rights)] バラ科サクラ属に属する植物の葉の抽出液を含有する抗腫瘍製剤 (2016)
  • Inventor(s): 塩田清二
  • Industrial Property Rights Holder: 塩田清二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-06-30
• [Patent(Industrial Property Rights)] 生物由来液取得方法 (2016)
  • Inventor(s): 塩田清二
  • Industrial Property Rights Holder: 塩田清二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-06-30