一般ポスター

一般ポスター神経系疾患と治療

7月8日（土）　12:50-13:50　ポスター会場① 3P⑤-1 ヒト歯髄細胞の抗酸化活性と脊髄損傷モデルへの移植治療効果に関する研究 Characterization of human dental pulp cell clones, antioxidant activity, and effects on rodent spinal cord injury 福光　秀文¹, 中村　海斗¹, 長島　光介¹, 山田　まこと¹, 小林　洋之¹, 手塚　建一², 宗宮　仁美¹ 1. 岐阜薬科大学　生体機能解析学大講座　分子生物学研究室, 2. 岐阜大学大学院　医学系研究科　再生機能医学分野 Fukumitsu Hidefumi¹, Kaito Nakamura¹, Kosuke Nagashima¹, Makoto Yamada¹, Hiroyuki Kobayashi¹, Ken-ichi Tezuka², Hitomi Soumiya¹ 1. Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, 2. Department of Stem Cells and Regenerative Medicine, Gifu University Graduate School Of Medicine Our laboratory has been studying the effects of transplantation of human dental pulp cells (DPC) on rodent models with spinal cord injury (SCI). In this study, using several human dental pulp-derived cell clones, we characterized each individual DPC clone; the therapeutic effects on SCI after transplantation, cell migration, resistance to ROS, and expression of antioxidant factors. We found 4 donor-derived DPC clones showing significant recovery of locomotor function in the hindlimbs of rats with complete SCI after cell transplantation, whereas 3 donor-derived DPC clones did not show sufficient efficacy. The correlation of each parameter suggested that resistance to H2O2 toxicity is likely to be an important factor for the DPC clone to improve the locomotor functions of SCI rats after transplantation. Next, we examined the expression of several antioxidant factors and found a positive correlation between the expression of antioxidant factor X and resistance to H2O2 toxicity. In addition, we examined the effect of a chemical treatment on donor-derived DPC clones activating nuclear factor E2-related factor 2 (Nrf2), the master regulator of antioxidant enzymes, and found that the Nrf2 activator treatment increased resistance to H2O2 in each DPC clone examined. We are currently examining the effect of Nrf2 activator-treated cells on the SCI model.		7月8日（土）　12:50-13:50　ポスター会場① 3P⑤-2 PACAP KOマウスの多動性と軸索起始部の形態に対するADHD治療薬の影響 Effects of ADHD medication on hyperactivity and morphology of axon initial segment in PACAP knockout mice 張替　若菜¹, 吉村　武¹, 早田　敦子^1,2,3, 岩橋　美咲¹, 藤原　悠紀¹, 三好　耕¹, 田熊　一敞^1,3, 橋本　均^1,2, 片山　泰一¹ 1. 大阪大学　連合小児, 2. 大阪大学薬学, 3. 大阪大学　歯学 Wakana Harigai¹, Takeshi Yoshimura¹, Atsuko Hayata^1,2,3, Misaki Iwahashi¹, Yuuki Fujiwara¹, Ko Miyoshi¹, Kazuhiro Takuma^1,3, Hitoshi Hashimoto^1,2, Taiichi Katayama¹ 1. UGSCD, Osaka Univ., Osaka, Japan, 2. Grad. Sch. Pharm. Sci., , Osaka Univ., Osaka, Japan, 3. Grad. Sch. Dent., Osaka Univ., Osaka, Japan ADHDとは不注意、多動性、衝動性を特徴とする脳機能障害である。Pituitary adenylate cyclase-activating polypeptide（PACAP）は脳に広く発現し、神経保護作用などを示す神経ペプチドである。PACAP knockout（KO）マウスは多動性や頻繁なジャンプ行動などの行動異常を示し、この多動性には注意欠如多動症（ADHD）治療薬が有効である。昨年度、我々は多動性や衝動性を示す複数のげっ歯類モデルにおいて、活動電位の出力部位である軸索起始部の長さの変化を見出した。しかし、軸索起始部の長さの変化と行動異常との関わりは不明である。そこで、本研究ではPACAP KOマウスにADHD治療薬を投与し、多動性が改善する際の軸索起始部の長さの変化について検討したので、その結果を報告する。

7月8日（土）　12:50-13:50　ポスター会場① 3P⑤-3 マウス脳内出血病態に対するmenaquinone-4の効果 Effect of menaquinone-4 on the pathology of intracerebral hemorrhage in mice 牛田　啓介¹, 木下　慶大¹, 倉内　祐樹¹, 関　貴弘², 香月　博志¹ 1. 熊本大学　薬　薬物活性学, 2. 姫路獨協大学　薬学部　薬理 Keisuke Ushida¹, Keita Kinoshita¹, Yuki Kurauchi¹, Takahiro Seki², Hiroshi Katsuki¹ 1. Department of Chemico-Pharmacological Sciences Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan, 2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Himeji Dokkyou University Intracerebral hemorrhage (ICH) is a disease with poor prognosis including high mortality and severe motor dysfunction, resulting from expanded inflammatory responses and loss of neurons in the brain. Menaquinone-4 (MK-4), which belongs to the vitamin K2 group, has been noted for its antioxidant and cytoprotective effects. It is reported that MK-4 exhibits neuroprotective roles and improves motor function after cerebral ischemia/reperfusion injury, but the effect for ICH is unclear. Here we investigated the effects of MK-4 on pathological parameters of ICH in mice. MK-4 (200 mg/kg) was administered at 3 h after ICH induction and twice every 24 h thereafter. We observed that motor dysfunction after ICH was ameliorated in the MK-4 group compared to the control group. Moreover, MK-4 reduced axonal tract injury at 1 and 3 d after ICH in the internal capsule containing the corticospinal tract and tended to suppress demyelination at 3 d after ICH. Furthermore, MK-4 suppressed increased expression of heme oxygenase-1 (HO-1), an oxidative stress indicator, in the peri-hematoma region at 3 d after ICH. These results demonstrated that MK-4 provides a therapeutic effect on motor dysfunction associated with ICH, and that reduction of axonal injury and regulation of oxidative stress response may contribute to its therapeutic effect.		7月8日（土）　12:50-13:50　ポスター会場① 3P⑤-4 大脳皮質梗塞ラットにおける超早期リハビリテーションによる炎症性因子発現の変化 Inflammatory factor expression alteration by very early rehabilitation in rats with cortical infarction 玉越　敬悟, 斎藤　愛海, 渡部　朱音, 本山　雅大, 有岡　航新潟医福大　理学療法 Keigo Tamakoshi, Ami Saito, Akane Watanabe, Masahiro Motoyama, Wataru Arioka Dept. of Phys. Ther. Niigata Univ. of Health and Welfare This study examined very early exercise’s effects at 6 hours post-infarction on proinflammatory factors in rats with cortical ischemia (CIS). Subjects were randomly assigned to no training post CIS (CIS), no training after sham surgery (SHAM), and very early treadmill exercise post CIS (CIS + VET). CIS + VET performed treadmill exercise for 60 minutes at 6 hours post CIS. At 10 hours post CIS, the brain was removed and analyzed for lesion volume and proinflammatory factors. For analyzing proinflammatory factors, IL1b and TNFb protein expression levels were determined using ELISA. Additionally, 40 chemokine, 25 interleukin, 8 tumor necrosis factor, and 11 other inflammation related genes were analyzed using RT2 Profiler PCR Arrays (QIAGEN). Inflammatory factors were analyzed as cortical damage areas. Injury volume in the CIS + VET group was significantly higher than in the CIS group. TNFb protein expression showed a trend toward higher levels in the CIS + VET group compared to the SHAM group. Inflammation related genes in the CIS + VET group showed upregulation of CxCr1, Tnfsfl4, Ccl5, Ccr3, and Cd40lg and downregulation of Cxcl11, Cxcr5, Il11, Il7, Ccl20, Ccl9, and Cxcr2. The infarct volume expansion due to very early exercise post CIS may involve changes in the expression of inflammation-related factors, primarily in the chemokine system.

7月8日（土）　12:50-13:50　ポスター会場① 3P⑤-5 脳梗塞後の海馬歯状回で誘導されるArcadlinは樹状突起スパイン密度減少に関与する Arcadlin induction in the hippocampal DG is involved in dendritic spine density reduction after cerebral ischemia. 中澤　秀真, 井上　耀介, 井上　翔太, 山口　菜摘, 中谷　仁, 澤野　俊憲, 田中　秀和立命館大学大学院　生命科学研究科　薬理学研究室 Shuma Nakazawa, Yosuke Inoue, Shota Inoue, Natsumi Yamaguchi, Jin Nakatani, Toshinori Sawano, Hidekazu Tanaka Lab. Pharmacol., Grad. Sch. Life Sci., Ritsumeikan Univ The changes of dendritic spine morphology occur in the brain after cerebral ischemia. Arcadlin, a non-clustered protocadherin δ2, is induced by neuronal activity and reduces the dendritic spine density. Cerebral ischemia induces neuronal activity but the expression of Arcadlin and its role in the ischemic brain are not clear. In this study, we investigated Arcadlin expression and dendritic spine changes after cerebral ischemia using a highly reproducible mouse model of cerebral ischemia by performing middle cerebral artery occlusion (MCAO). We found that Arcadlin mRNA was significantly upregulated in the hippocampal dentate gyrus (DG) at 4 hours after MCAO. In the ipsilateral DG, dendritic spine density in MCAO mice was lower than that in sham mice. However, MCAO-induced reduction of dendritic spine density was partially alleviated by Arcadlin Knockout. These results suggest that Arcadlin is involved in the reduction in the dendritic spine density after cerebral ischemia.