一般口演

一般口演感覚と行動の分子基盤

7月6日（木）　10:00-11:00　Room D 1O④-1 Dystonia musculorumマウスが示す運動異常における感覚運動回路の役割 Role of sensory-motor circuit in the movement disorder in dystonia musculorum mice. 吉岡　望¹, 黒瀬　雅之², 佐野　裕美³, 知見　聡美⁴, 山村　健介⁵, 南部　篤⁴, 竹林　浩秀¹ 1. 新潟大学・医・神経解剖学, 2. 岩手医科大学・歯・病態生理学, 3. 藤田医科大学・精神・神経病態解明センター・神経行動薬理学, 4. 生理学研究所・生体システム, 5. 新潟大学・歯・口腔生理学 Nozomu Yoshioka¹, Masayuki Kurose², Hiromi Sano³, Satomi Chiken⁴, Kensuke Yamamura⁵, Atsushi Nambu⁴, Hirohide Takebayashi¹ 1. Div of Neurobiol and Anat, Grad Sch of Med and Dent Sci, Niigata Univ, Niigata, Japan, 2. Dep of Physiol, Sch of Dent, Iwate Med Univ., 3. Div of Behav Neuropharmacol, ICBS Proj Neuropsychol Res Cent, Fujita Health Univ., 4. Div of System Neurophysiol, Natl Inst for Physiol Sci., 5. Div of Oral Physiol, Grad Sch of Med and Dent Sci, Niigata Univ. Mutations in the dystonin (DST) gene encoding the cytoskeletal linker protein are causative for the hereditary sensory autonomic neuropathy VI (HSAN6), which is an inherited disease of the peripheral nervous system (PNS). Dystonia musculorum (dt) mice carrying Dst mutations exhibit ataxia and sensory neurodegeneration in the dorsal root ganglia (DRG). We generated multipurpose Dst gene-trap mice in which the gene-trap allele inverts from the mutant (DstGt) to functional (DstGt-inv) allele: conditional rescue (cRescue) and from functional (DstGt-inv) to mutant (DstGt-DO) allele: conditional gene-trap (cGT) by Cre-mediated recombination. To manipulate Dst expression in the PNS, Dst gene-trap mice were crossed with Wnt1-Cre transgenic mice in which Cre recombination occurred in neural crest cells and the hindbrain during the embryonic stages. As expected, Cre-mediated inversion of the Dst gene-trap allele occurred in DRG neurons. Wnt1-Cre;Dst cGT mice exhibited ataxia and pathological alternations in DRG neurons. Wnt1-Cre;Dst cRescue mice showed restoration of Dst expression in DRG neurons, amelioration of sensory neurodegeneration, and recovery from ataxia. We have found that abnormalities of the sensory-motor circuit correlate with the ataxic phenotype. These results have revealed that abnormalities of the sensory-motor circuit are crucial for movement disorder in dt mice.		7月6日（木）　10:00-11:00　Room D 1O④-2 第2世代のバルプロ酸胎内暴露自閉症モデルマウスの小児期における社会的コミュニケーションと自発運動異常は早期に発症する Early-onset of communicational and behavioral alterations in F2 pups of a mouse model of autism spectrum disorder 辻　隆宏¹, 辻　知陽¹ 1. 金沢大学子どものこころの発達研究センター, 2. 福井大学眼科学教室, 3. 福井大学ライフサイエンスイノベーションセンター Takahiro Tsuji¹, Chiharu Tsuji¹ 1. Research Center for Child Mental Development, Kanazawa University, 2. Department of Ophthalmology, Faculty of Medical Science, University of Fukui, 3. Life Science Innovation Center, University of Fukui Autism spectrum disorder (ASD) usually develops by age three, and the symptoms can last throughout life. Many mouse models of ASD have been reported, among which mice in utero exposure to valproic acid (VPA mice) have been widely used. Valproic acid acts epigenetically as a histone deacetylase. Recently, epigenetics has been suggested to contribute to the etiology of ASD, with the hypothesis that epigenetic marks are inherited across generations. Autistic characters in F1 VPA mice are taken over to F2 and F3 mice. However, their onset in F2 and F3 has not been studied yet. Therefore, this study examined the behavioral abnormalities in the F2 of VPA mice at 5 postnatal days (PND). Communication deficits were examined by analyzing maternal separation-induced ultrasonic vocalizations (USVs). The duration and frequency of USVs did not change significantly, but the rate of calls was significantly reduced in F2 VPA pups. Furthermore, locomotor activity was altered in F2 VPA pups with the presence or absence of their siblings. These results suggest that lack of social communication and reduced locomotion were inherited in subsequent generations and were evident as early as 5 PND.

7月6日（木）　10:00-11:00　Room D 1O④-3 マクロファージ-ニューロンのシグナル伝達は痛みの処理に重要である Macrophage-neuron signaling is important in pain processing in naive skin and in neuropathic or inflammatory situations 田中　達英, 石西　綾美, 辰巳　晃子, 和中　明生奈良医大　医　２解剖 Tatsuhide Tanaka, Ayami Isonishi, Kouko Tatsumi, Akio Wanaka Dept. Anat. Neurosci., Med., Nara Med. Univ. Sensory stimuli impinging on skin are encoded by peripheral sensory neurons that can be classified into low-threshold mechanoreceptors, which detect innocuous tactile stimuli, and nociceptors, which exclusively respond to harmful stimuli. Crosstalk between peripheral neurons and immune cells plays important roles in pain sensation. We identified sorting nexin 25 (SNX25) as a pain-modulating gene in a transgenic mouse line with reduced pain behavior. SNX25 conditional-KO (cKO) in monocyte/macrophage-lineage cells but not in the peripheral sensory neurons reduced pain responses in both normal and neuropathic conditions. Cross transplantation experiments of bone marrows between cKO and wild type (WT) mice revealed that cKO macrophages caused dull phenotype in WT mice and WT macrophages in turn increased pain behavior in cKO mice. SNX25 inhibited ubiquitination and proteasome degradation of a CNC-bZIP transcription factorNrf2, which regulated the transcription of Ngf mRNA and, as such, maintained the production of NGF in dermal macrophages. Loss of SNX25 accelerated Nrf2 degradation and lowered NGF expression, which led to insensitivity to pain. We conclude that dermal macrophages set pain sensitivity by producing and secreting NGF into the dermis in addition to their host defense functions.		7月6日（木）　10:00-11:00　Room D 1O④-4 がん化学療法に伴う味覚嫌悪の解析 Analysis of taste aversion associated with Cancer chemotherapy 小山　佳久¹, 清水　多聞¹, 島田　昌一^1,2 1. 大阪大学大学院医学系研究科神経細胞生物学, 2. 大阪精神医療センターこころの科学リサーチセンター依存症ユニット Koyama Yoshihisa¹, Shimizu Tamon¹, Shoichi Shimada^1,2 1. Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine Cancer chemotherapy is a systemic therapy that is effective against cancer developed systemic metastasis and prevents recurrence. However, side effects such as kidney damage, neuropathy and nausea are likely to occur. Especially, taste aversion (TA) leads to weight loss, malnutrition, and decreased physical strength due to decreased appetite and markedly reduces quality of life even after the end of chemotherapy. The development of therapeutic drugs for TA is urgently needed, but the detailed mechanism is unknown. Therefore, to elucidate the action mechanism of TA, we prepared a new mouse model of TA caused by anticancer drug administration.When a two-bottle test of saccharin-containing water (sac water) and simple water was conducted, normal mice preferred to drink sac water. However, cisplatin-treated mice avoided sac water and drank more simple water. Since TA did not occur when sac water was given one day after cisplatin administration, it is considered that conditioning was established between the cisplatin administration and the drink ingested at the same time. Surprisingly, the acquired TA learning was retained for 3 months. We succeeded in establishing a long-term TA mouse model.In this presentation, I would like to discuss the research results and future prospects.