一般演題（ポスター）

一般演題（ポスター） Neural Metabolism

3P-22 Setpoint of core body temperature is remodeled prior to hibernation in a obligatory hibernator, Mesocricetus auratus. Chayama Yuichi¹，Ando Lisa¹，Miura Masayuki^1,2，Yamaguchi Yoshifumi^1,3 ¹Department of Genetics, Graduate school of Pharmaceutical sciences, the University of Tokyo，²CREST, JST，³PRESTO, JST Hibernation is a strategy with profound suppression of metabolic rate, motility, and body temperature in order to avoid energy wastes and survive severe winter or harsh environment with a little or no food. It has been suggested that mammalian hibernators remodel their body to develop tolerance against many types of stresses including severe hypothermia, starvation, ischemia-reperfusion injury, and obesity, in the pre-hibernation period, whereas physiological and molecular mechanisms of such adaptive remodeling remain largely unclear. To identify when and how the adaptive remodeling starts during the pre-hibernation period, we utilize syrian golden hamster（Mesocricetus auratus）, which initiates hibernation after prolonged exposure to short day and cold acclimation condition（about 4~12 weeks）. We found that a core body temperature（Tb）was decreased after 8 weeks of exposure, which preceded entrance into hibernation, suggesting that a setpoint of Tb started to be lowered during pre-hibernation period and minimized in hibernation period. The remodeling of Tb setpoint and the efficiency of hibernation induction were affected by animals’body weight. These observations suggest that lowering Tb setpoint is one of crucial aspects of the adaptive remodeling that precedes hibernation induction.		3P-23 Analyses of metabolic changes of neurons using cultured hippocampal slices Hasegawa Sho¹，Okahashi Nobuyuki²，Matsubara Takashi³，Tominaga-Yoshino Keiko¹，Isii Kojiro⁴，Simizu Hiroshi²，Ogura Akihiko¹ ¹Laboratory of Synaptic Plasticity, Graduate School of Frontier Biosciences, Osaka University，²Laboratory of Metabolic Engineering, Graduate School of Information Science and Technology, Osaka University，³Department of Computational Science, Graduate School of System informatics, Kobe University，⁴Laboratory of Chromosome Function and Regulation, Graduate School of Frontier Biosciences, Osaka University Metabolic changes of the brain have been analyzed as indices for neuronal activity. For examples, the reduced glucose（Glc）consumption and the increased lactic acid（LA）production in the patient of Alzheimer disease are regarded indices of lowered neuronal activity and of disordered oxygen supply, respectively. However, those interpretations may include prejudice. To know the cellular bases of those metabolic changes, we monitored here those changes by HPLC using the hippocampal slice culture that preserves neuronal circuit but allows pharmacological interventions. Induction of LTP with forskolin did not produce significant changes in either Glc consumption or LA production. However, 3 repeated inductions of LTP, known to produce a long-lasting synaptic enhancement coupled with synaptogenesis, brought about an increased Glc consumption leaving LA production unaltered. An application of bicuculline, known to produce epileptic excitation, brought about increases in both Glc consumption and LA production. Those results indicate that the increase in Glc consumption indicates physiologically elevated neuronal activity, while that in LA production indicates pathologically elevated activity. In the cultured slice, the activation of metabotropic glutamate receptor induces LTD and the repeated induction of LTD leads to a long-lasting synaptic suppression coupled with synapse elimination. Neither single LTD nor repeated LTD evoked the changes in Glc consumption and LA production, suggesting that the repetitive-LTD-operated synapse suppression is a physiological process.

3P-24 Shati/Nat8l induces axon outgrowth via energy metabolism in the primary cultured neurons of mice Nitta Atsumi¹，Sumi Kazuyuki¹，Uno Kyosuke¹，Matsumura Shohei¹，Miyamoto Yoshiaki¹，Furukawa-Hibi Yoko²，Muramatsu Shin-ichi³，Nabeshima Toshitaka⁴ ¹Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama，²Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine，³Division of Neurology, Department of Medicine, Jichi Medical University，⁴Nabeshima Laboratory, Faculty of Pharmacy, Meijo University We have identified a novel molecule, Shati/Nat8l in the nucleus accumbens（NAc）of mice repeatedly treated with methamphetamine（METH）. Shati/Nat8l produces N-acetylaspatate（NAA）from aspartate and acetyl-CoA. Previously we reported that overexpression of Shati/Nat8l in NAc attenuates the response to METH via N-acetylaspartylglutamate（NAAG；which is derived from NAA）-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in situ hybridization for the detection of Shati/Nat8l mRNA accompanied by immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain；then, we used adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary hippocortical neurons to investigate the contribution to neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary hippocortical neurons induced axonal growth but not dendrite elongation at day 1.5（DIV）. This finding indicated that Shati/Nat8l contributes to neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and NAAG itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth via ATP synthesis and not through mGluR3 signaling.		3P-25 LAMP2C, a receptor for novel lysosomal RNA/DNA degradation systems, possesses an arginine-rich motif that mediates RNA/DNA-binding Fujiwara Yuuki，Hase Katsunori，Wada Keiji，Kabuta Tomohiro Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry Degradation of macromolecules by lysosomes is a fundamental event for biological homeostasis in cells and tissues including neurons and brain. Neurons are cells rich in RNA, and aberrant function and accumulation of RNAs in neurons are reported to cause various neurodegenerative diseases. Degradation of cellular RNA can be an important issue for the better understanding of homeostasis of neuron and pathogenesis of such diseases. We previously discovered novel lysosomal degradation systems in which RNA and DNA are directly imported into lysosomal lumen and degraded. These systems, which we termed RNautophagy/DNautophagy（hereafter abbreviated as RDA）, are ATP-dependent and a lysosomal membrane protein, LAMP2C was identified as at least one of receptors for both RNA and DNA. In this study, we examined the mechanisms underlying recognition of nucleic acids by LAMP2C. We found that the cytosolic sequence of LAMP2C possesses features of the arginine-rich motif, a well-known RNA-recognition motif found in a wide range of RNA-binding proteins. Substitution of arginine residues in the cytosolic sequence of LAMP2C completely abolished its binding ability to both RNA and DNA. A scrambled form of the sequence showed affinity to both nucleic acids equivalent to that of the wild-type sequence, as is the case for other arginine-rich motif. In addition to these results, we also found that cytosolic sequences of other LAMP family proteins, LAMP1 and CD68/LAMP4, also possess multiple arginine residues, and show affinity for nucleic acids. Together with the fact that RDA activity is not completely abolished in lysosomes derived from LAMP2 deficient mice, these results suggests the existence of other receptors in RDA. Our results provide further insight into the mechanisms underlying RDA, and may contribute to a better understanding of lysosome function. We would also like to discuss physiological roles of RDA and their possible involvement in diseases.

3P-26 The protective effects of high dose adenosine deaminase during oxygen glucose deprivation on rat corticostriatal slices. TAMURA RISA¹，Ohta Hiroyuki¹，Nibuya Masashi²，Sato Yasushi³，Nishida Yasuhiro¹ ¹Department of physiology, NDMC，²Psychiatry, NDMC，³Anesthesiology, NDMC Adenosine increase in response to ischemic brain insults and adenosine receptors are one of the main therapeutic targets. However, some controversy remain regarding to adenosine effects in striatum, where abundant A2aR receptors exist and A2aR antagonists have been shown to be either protect or increase striatal damage. In the present study, we demonstrate that striatal neuroprotection induced by adenosine deaminase（ADA）（EC 3.5.4.4）, the enzyme catabolizes deamination of adenosine to inosine and ammonia and decrease adenosine concentration. We used the oxygen/glucose deprivation（OGD）for 10 minutes as model of ischemia in corticostriatal brain slices. In electrophysiological assessment, we used adult Wistar Thy-1.2 promoter channelrhodopsin-2 Venus transgenic rats of both sexes to enable optgenetical evaluation. We recorded time course of corticostriatal extracellular field potential（FP）evoked via a bipolar stimulating electrode placed in the corpus callosum as well as striatal field potential evoked by optogenetic stimulation to striatum（fOPT）. In control group, 30 minutes after OGD, FP and fOPT were decreased. Application of the ADA in artificial cerebrospinal fluid during OGD significantly suppresses the OGD induced reduction. In histological evaluation, dead cell counts with propidium iodide also support this protective effect. These results show that ADA plays a neuroprotective role in corticostriatal pathway.