一般口演（Oral）

Oral Neurotransitters 一般口演神経伝達物質

7月25日（木）10:00～10:15　第9会場（朱鷺メッセ　3F　306+307） 1O-09m2-1 加齢に伴う神経伝達物質濃度の変化：7TMRスペクトロスコピーによる研究 Toru Ishii（石井徹）¹，Koji Fujimoto（藤本晃司）¹，Dinh Ha Duy Thuy（Thuy Dinh）¹，Hideto Kuribayashi（栗林秀人）²，Yuta Urushibata（漆畑勇太）²，Tadashi Isa（伊佐正）¹，Tomohisa Okada（岡田知久）¹ ¹京都大学大学院医学研究科附属脳機能総合研究センター ²シーメンスヘルスケア INTRODUCTION: Some previous reports have shown that alterations of the excitation/inhibition balance in the brain are associated with age-related cognitive decline. As a premise for investigating the neurodegenerative process, to understand neurochemical changes in the brain associated with normal aging is indispensable. Proton magnetic resonance spectroscopy (MRS) is a promising method for such a purpose as it can noninvasively assess neurochemical concentrations in vivo. However, the results of previous studies using MRS at 1.5T or 3T are not necessarily consistent, and the metabolic changes across life span still remain to be elucidated. The purpose of this study was to quantify changes of neurochemical concentrations related to aging with high sensitivity and accuracy using an ultra-high field 7T-MRI system. METHODS: Seventy-four healthy adults (38 females, age;50.8 ± 21.4, range; 20-77 years) who had no history of any neurological or psychiatric disorders were enrolled. MRS was scanned with a 7T scanner (Magnetom 7T, Siemens). A 20-mm cubic volumes-of-interest was positioned at the posterior cingulate cortex. Proton MR spectra were acquired using a stimulated echo acquisition mode (STEAM) sequence (research prototype) with short echo time (TR = 8000 ms, TE = 5 ms) with water and outer volume suppressions. All spectra were analyzed using LCModel. Associations between age and neurochemical concentrations were analyzed by linear regression. RESULTS: Concentrations of Glutamate and GABA showed significant negative correlation with age (P < 0.05). These correlations remained significant after discarding individual data with CRLB ≧ 20%. Meanwhile, concentrations of total Creatine and myo-Inositol positively correlated with age. DISCUSSION: In line with some previous reports, our results showed that myo-Inositol, which is thought to be a glial marker, increases with age. Moreover, the results showed that both of the main excitatory and inhibitory neurotransmitters in the brain, Glutamate and GABA, significantly decrease with aging. Reduction of Glutamate and GABA with aging might reflect not only the results of nonspecific neuronal loss but alterations in regulation of synaptic function. The results shed light on changes in human brain associated with normal aging and will contribute to elucidate disease-specific neurodegenerative process.		7月25日（木）10:15～10:30　第9会場（朱鷺メッセ　3F　306+307） 1O-09m2-2 ラット海馬スライスにおけるカルバコール誘発ベータ振動によるてんかん様発火の抑制におけるアデノシンA 1受容体の関与 Toyohiro Sawada（澤田豊宏），Kiyohisa Natsume（夏目季代久）九州工業大学生命体工学研究科 Epilepsy is the most susceptible to neurological diseases. The suppression of the onset of the epilepsy in rapid eye movement period when theta rhythm is induced remains controversial. Our previous work found that hippocampal beta rhythm will suppress the onset of epilepsy. Beta rhythm is intermittently induced in rat hippocampal slices with the application of the cholinergic agent carbachol (CCh). The rhythm is called CIBO. The epileptic discharges are induced with the application of GABAA receptor antagonist to hippocampal slices. Our previous work indicated that GABAA antagonist-induced epileptic discharges (GIED) were not induced when CIBO was induced with the application of 30 μM carbachol. CCh at the lower concentration didn't induce β oscillation and then GIED was induced. Therefore, CIBO itself might suppress GIED. In the present study, we have studied the involvement of adenosine A1 receptor in CIBO-induced suppression of GIED. The data were obtained from hippocampal slices (450-μm thick) of 5 male Wistar rats. The recording glass electrode (< 2 MΩ) was placed in the CA3 stratum pyramidale. Carbachol at 30 μM induced CIBO. Thirty minutes after the generation of CIBO, the selective antagonist of adenosine A1 receptor, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was applied to CIBO. It prolonged inter-burst interval (IBI) of CIBO. Then GABAA receptor antagonist SR-95531(GABAzine) was administered to CIBO. Then GIED was induced and was facilitated. These results suggest that the activation of adenosine A1 receptor will suppress the onset of GIED in the generation of CIBO. The modulation of the adenosine A1 receptor activation in the generation of theta or beta rhythm may determine whether the epilepsy is started or not.

7月25日（木）10:30～10:45　第9会場（朱鷺メッセ　3F　306+307） 1O-09m2-3 忌避行動・学習に至る側坐核内のアセチルコリンの作用機序 Yukie Yamahashi（山橋幸恵）¹，Shou Iwanaga（岩永渉）¹，Yuya Tokumoto（徳元友哉）¹，You-hsin Lin（林祐新）¹，Xijian Zhang（張心健）¹，Taku Nagai（永井拓）²，Daisuke Tsuboi（坪井大輔）¹，Kozo Kaibuchi（貝淵弘三）¹ ¹名古屋大学大学院医学系研究科神経情報薬理学 ²名古屋大学大学院医学系研究科細胞情報医学専攻医療薬学 Acetylcholine is a critical neuromodulator for the formation of aversive learning. Due to the reduced acetylcholine level in the patient's brain, it is known to be associated with Alzheimer's disease, which shows impaired aversive learning. The therapeutic drug recovers the acetylcholine level by inhibiting acetylcholinesterase that catalyzes the breakdown of acetylcholine, thereby improving the learning deficits in the disease. However, the therapeutic drug does not completely cure, as the mode of acetylcholine in neurons has not been clarified yet. Based on that acetylcholine level is thought to be the highest in striatum/nucleus accumbens (NAc), which impacts aversive learning, in this study we aimed to clarify the mode of action of acetylcholine in striatum/NAc. Striatum/NAc consists mainly of medium spiny neurons that express dopamine D1 receptor (D1R-MSN) and dopamine D2 receptor (D2R-MSN). D2R-MSN is critical in aversive learning. Recent studies have shown that acetylcholine preferentially activates D2R-MSN, whose activation is suggested to be mediated through muscarinic receptor M1 (M1R). Based on that M1R activates its downstream mediator protein kinase C (PKC), we here focused on the M1R-PKC pathway that leads to aversive learning. By exploiting our phosphoproteomics system for comprehensive PKC substrate screening, we identified 116 PKC substrate candidates, including Rho family GTPase Rac activator βPIX. We also found that acetylcholine enhances βPIX phosphorylation by PKC, thereby activating Rho family GTPase Rac and its downstream effector PAK kinase, a potential therapeutic target for neuropsychological diseases. Furthermore, in Cre-Flex system, we found that the activated Rac-PAK signaling by acetylcholine in D2R-MSN contributes to aversive learning. This study would shed light to the molecular basis of Alzheimer's disease.		7月25日（木）10:45～11:00　第9会場（朱鷺メッセ　3F　306+307） 1O-09m2-4 進化的に保存された痛覚の抑制調節を担うショウジョウバエの神経ペプチド経路 Izumi Oikawa（及川泉）¹，Shu Kondo（近藤周）²，Akiho Kashiwabara（柏原秋穂）¹，Hiromu Tanimoto（谷本拓）³，Katsuo Furukubo-Tokunaga（古久保－徳永克男）¹，Ken Honjo（本庄賢）¹ ¹筑波大院　生命環境科学 ²国立遺伝研 ³東北大院生命科学 Nociception, a neural process detecting tissue-damaging stimuli, is a crucial sensory function for animals to survive. Since nociception often leads to a perception of pain in humans, a better understanding of the mechanisms underlying nociception crucial to develop better treatment for pain. Among the molecules controlling nociception, neuropeptides have been known to play important roles in the transmission and regulation of nociception signaling. However, due to the complexity of the neuropeptide systems in mammals, elucidation of how neuropeptides control nociception has been a challenging task. In order to study detailed mechanisms of neuropeptide functions, Drosophila is a very suitable model organism. Since the neuropeptide systems are well conserved between flies and humans, new findings in Drosophila will provide useful insights toward a comprehensive understanding of neuropeptide functions in humans. In addition, Drosophila has been serving as an attractive model system to study molecular mechanisms of nociception, with its powerful genetic tools and straightforward behavioral paradigm. Through genetic screens, we have identified an evolutionarily conserved neuropeptide that negatively regulates nociception in Drosophila. Because studies of its cognate neuropeptide in mammals suffer from contradicting data, exact functions of this neuropeptide in nociceptive regulation remain unclear. Here we show that deleting the genes encoding either the neuropeptide or its receptors leads to thermal hyperalgesia, suggesting that the signaling system of this neuropeptide functions as a negative regulator of nociception in Drosophila. By expression analyses either with the highly reliable GAL4 or immunological staining, we have found that receptors of this neuropeptide are expressed in a subset of the previously identified nociceptive interneuron. Furthermore, RNAi experiments showed that knocking down one type of receptors expression in that nociceptive interneuron led to hypersensitive, raising a possibility that this neuropeptide may downregulate nociceptive signaling by suppressing the activities of nociceptive interneurons. Calcium imaging experiments to reveal how this neuropeptide affects the neuronal activities of the nociceptive interneurons are currently ongoing, and the latest data will be included in the presentation.