一般口演
グリア・神経回路 |
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| 7月8日（土） 13:50-14:50 Room E
3O①-1
EGFシグナルはマウス大脳皮質においてペリニューロナルネットの形成を阻害する
Epidermal growth factor (EGF) signal modulates perineuronal net formation in the neocortex of developing rodent brains.
岩倉 百合子1,4, 小林 雄太朗2,4, 難波 寿明3,4, 那波 宏之3,4, 武井 延之1,4
1. 新潟大 脳研 腫瘍病態学, 2. 九州大 生体防御医学研 システム免疫学統合研究センター アレルギー防御学, 3. 和歌山県医大 薬学部 生体機能解析学, 4. 新潟大 脳研 分子神経生物学
Yuriko Iwakura1,4, Yutaro Kobayashi2,4, Hisaaki Namba3,4, Hiroyuki Nawa3,4, Nobuyuki Takei1,4
1. Dept. of Brain tumor biology, Niigata Univ. Brain Res Inst., Niigata, Japan, 2. Div of Allergy and Immunology, Kyushu Univ. Med Inst. of Bioregulation. Fukuoka, Japan, 3. Dept of Physiological Sciences, School of Pharmaceutical Sci, Wakayama Med Univ. Wakayama, Japan, 4. Dept. of Brain tumor biology, Niigata Univ. Brain Res Inst., Niigata, Japan
Perineuronal nets (PNNs) are formed on GABAergic neurons along with their development and are constructed mainly by chondroitin sulfate (CS) proteoglycans (CSPGs). In the present study, we examined the EGF effects on CSPG production and PNN formation. In the EGF-overexpressing transgenic (EGF-Tg) mice, the number of the PNN-positive neurons, and the amount of CS and CSPG neurocan were significantly decreased in the cortex compared with those in wild-type mice. A similar decreasing trend was exhibited in the EGF-treated cultured cortical neurons. An EGF receptor kinase inhibitor, PD153035, blunted the above EGF-triggered PNN reductions. We explored the molecular mechanism underlying the EGF effects on PNNs, using positive-charged fluorescent particles which presumably bind to the negative sulfate-moiety of CS of PNNs. EGF disrupted the accumulation of the particles around GABAergic neurons but rather scattered from them. EGF increased CS contents in the culture supernatants of primary glia whereas it elevates the enzyme activity of matrix metalloproteinases (MMPs) in cultured neurons. These results suggest the possibility that EGF enhanced the MMP-dependent degradation or modification of CSPG in PNNs leading to the abnormal distribution of the fluorescent particles. Based on these results, EGF/EGF receptor signals may regulate PNN formation in the developing cortex. | | 7月8日（土） 13:50-14:50 Room E
3O①-2
カドヘリン6は大脳皮質発生においてニューロンの放射状移動を制御する
Cadherin-6 controls radial migration of neurons during neocortical development
廣田 ゆき1, 齋藤 里香穂1, 本田 岳夫1,2, 佐野 ひとみ1,3, 仲嶋 一範1
1. 慶應義塾大学医学部解剖学, 2. 岐阜薬科大・生体機能解析学・分子生物学, 3. システム・バイオロジー研究機構
Yuki Hirota1, Rikaho Saito1, Takao Honda1,2, Hitomi Sano1,3, Kazunori Nakajima1
1. Dept. of Anat., Keio Univ. Sch. Med.
During neocortical development, neuronal migration and birthdate-dependent positioning of neurons (layer formation) are highly regulated by multiple signaling cascades, including the cell adhesion molecules. We searched for the cadherins expressed in migrating neurons in the developing neocortex and focused on the Cdh6. Knockdown (KD) of Cdh6 impaired neuronal migration in the IZ. Cdh6 is known to bind to integrin through the arginine-glycine-aspartic acid (RGD) motif and controls integrin-mediated adhesion in some cancer cells. Migration defects caused by Cdh6 KD was restored by the expression of wild-type Cdh6, but not by Cdh6 with a mutated RGD motif. In vitro experiments showed that both Cdh6 KD in neurons and treatment of neurons with Cdh6 altered the amount of activated integrin β1 on neurons. These results suggest that Cdh6 controls neuronal migration via regulation of integrins. | | 7月8日（土） 13:50-14:50 Room E
3O①-3
アストロサイト間の細胞内温度についての解析
Analysis of intracellular temperature among astrocytes.
柴崎 貢志, 立石 周
長崎県立大学 栄養健康学科 細胞生化学研究室
Koji Shibasaki, Amane Tateishi
Lab Neurochem, Dep of Nutrition Science, Univ of Nagasaki
Cellular functions are fundamentally regulated by intracellular temperature, which influences biochemical reactions through thermosensitive proteins such as thermos-TRP channels. Despite the important contributions to biological and medical applications, the intracellular temperature mapping has not been achieved. Here we demonstrate the first intracellular temperature mapping in astrocytes based on a fluorescent polymeric thermometer by a ratio metric fluorescence imaging method. We found that some of specific astrocytes constitute cold cell populations, whose temperature is less than environmental temperatures. These results indicate that the cold populations might be endothermic astrocytes to effectively maintain the brain temperature, and showed that our new intracellular thermometry could determine specific relationship among astrocytes.We previously reported that TRPV4 is expressed in ~30% subpopulation of astrocytes in brain, and the TRPV4 activation leads to gliotransmitter (ATP and glutamate) release and increases synaptic transmission (Shibasaki et al. JBC 2014, J. Anesth 2016). It has been reported that TRPV4 is activated by various stimuli such as body temperature (>34°C). Thus, the TRPV4 activation properties might be different between cold astrocytes and normal cells. | | 7月8日（土） 13:50-14:50 Room E
3O①-4
哺乳類組織のイノシトールピロリン酸解析から明らかになったイノシトール7リン酸の腸管神経系分化と機能への役割
Inositol pyrophosphate profiling reveals regulatory roles of enhanced IP6K2-IP7 pathway in the enteric nervous system
伊藤 誠敏1,2, 藤井 奈津子1, 小原 さおり1, 堀 秀帆3, 田中 政之3, 垣本 由布4, 黒滝 大翼5, サイアルジ アドルフォ6
1. 東海大学 医学部内科学系 脳神経内科, 2. 聖マリアンナ医科大学 法医学教室, 3. 東海大学 生命科学統合支援センター, 4. 東海大学 医学部基盤診療学系 法医学教室, 5. 熊本大学 国際先端医学研究機構 免疫ゲノム構造学研究室, 6. ユニバーシティ・カレッジ・ロンドン 分子細胞生物学研究室
Masatoshi Ito1,2, Natsuko Fujii1, Saori Kohara1, Shuho Hori3, Masayuki Tanaka3, Yu Kakimoto4, Daisuke Kurotaki5, Adolfo Saiardi6
1. Deparment of Neurology, Tokai University School of Medicine, Japan
Inositol pyrophosphate IP7 regulates diverse physiological processes including central nervous system functioning. In this study, we measured IP7 levels in mammalian organs using an originally-designed LC-MS/MS, and discovered that the gastrointestinal tract (GIT) contained the highest levels of IP7. Of the major GIT cells, enteric neurons selectively express the IP7-synthesizing enzyme IP6K2. Consistently, the muscularis externa of IP6K2-/- proximal GIT significantly impairs IP7 metabolism. Its RNA sequencing analysis further displayed altered expression of gene sets associating with mature neuron, neural progenitor/stem cells, and glial cells as well as of transcription factors contributing to neural crest cell differentiation. These results demonstrate that a highly active IP6K2-IP7 pathway plays a regulatory role in the development and function of the enteric nervous system. | |
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