11:10-12:00, Rm 103

NeuroscienceH-17-01N-Adamantyl-4-methylthiazol-2-amine suppresses lipopolysaccharideinducedinflammation through regulation of NF-κB and ERK signalingpathways in neuronal cellsEun-A Kim¹ , ², Seung Cheol Ha¹, Hyo Jeong Son¹, Jiyoung Choi¹, Tae Ue Kim²,Soo Young Choi³and Sung-Woo Cho¹¹Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine,Seoul 138-736, Korea, ²Department of Biomedical Laboratory Science, Yonsei University, Wonju222-701, Korea, ³Department of Biomedical Science, Research Institute for Bioscience andBiotechnology, and Medical & Bio-material Research Center, Hallym University, Chunchon 200-702, KoreaMicroglia plays an active role in host defense and repair in the central nervous system.The activation of microglia is a crucial event associated with the neurodegeneration seenin many neuroinflammatory pathologies. We have examined various thiazole derivativesin cultured neuronal cells with a view to developing effective anti-neuroinflammatorydrugs. Thiazole derivatives are attractive candidates for drug development, because theyare useful in the treatment of various diseases, including neurodegenerative disorders. Inthis study, we show effects of a new drug, N-adamantyl-4-methylthiazol-2-amine againstlipopolysaccharide-induced inflammation in cultured neuronal cells. The drug preventedlipopolysaccharide-induced activation of microglia and production of proinflammatorymediators such as tumor necrosis factor-α, interlukin-1β, nitric oxide, and inducible nitricoxide synthase. In addition, the drug effectively attenuated the lipopolysaccharideinducedactivation of the NF-κB, ERK, and JNK pathways. These results support thepotential anti-neuroinflammatory efficacy of N-adamantyl-4-methylthiazol-2-amine via thetargeting of key glial activation pathways.H-17-02Neuroprotective effects of 2-cyclopropylimino-3-methyl-1,3-thiazolinehydrochloride against oxidative stressEun-A Kim¹ , ², Hyo Jeong Son¹, Seung Cheol Ha¹, Jiyoung Choi¹, Tae Ue Kim²,Soo Young Choi³and Sung-Woo Cho¹¹Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine,Seoul 138-736, Korea, ²Department of Biomedical Laboratory Science, Yonsei University, Wonju222-701, Korea,³Department of Biomedical Science, Research Institute for Bioscience andBiotechnology, and Medical & Bio-material Research Center, Hallym University, Chunchon 200-702, KoreaOxidative stress, glutamate excitotoxicity, and inflammation are important pathologicalmechanisms in ischemia. Very recently, we have reported that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects rat glial cells against glutamate-inducedexcitotoxicity. In this study, we report the effects of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride on primary cultured cortical neurons after exposure to hydrogenperoxide (H₂O₂). Pretreatment of cells with 2-cyclopropylimino-3-methyl-1,3-thiazolinehydrochloride prior to H2O2 exposure attenuated the H₂O₂-induced reduction in cellsurvival, activities of superoxide dismutase (SOD), glutathione (GSH), and glutathioneperoxidase (GSH-px) and the H2O2-induced increased levels in oxygen species (ROS),malondialdehyde (MDA) contents, nitric oxide (NO) productions, and thiobarbituric acidreactive species (TBARS) production in a concentration-dependent manner. Our resultssuggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects againstoxidative stress.H-17-04An endogenous substance in the mevalonate pathway facilitates TRPV3ion channel activation leading to nociceptionSangsu Bang, Sungjae Yoo, Tae-Jin Yang and Sun Wook HwangKorea University Graduate School of Medicine, Seoul 136-705, KoreaSensory neuronal or epidermal transient receptor potential ion channels (sensory TRPs)play an important role as peripheral pain sensors. Little is known about naturally occurringmolecules in our body, activating TRPV3, a member of the sensory TRPs. Here we showthat an intermediate lipidergic substance, farnesyl pyrophosphate (FPP) in themevalonate metabolism specifically activates TRPV3 using Ca2+ imaging andelectrophysiology with cultured keratinocytes and a HEK cell heterologous expressionsystem. Our single channel patch clamp recording data suggest that FPP binds to anextracellular binding site of TRPV3. Agonistic effects of other intermediates in the samemetabolism were ignorable. Voltage-dependence of TRPV3 was left-shifted under thepresence of FPP, which seems to be the activation mechanism. Peripheral administrationwith FPP evoked nocifensive behaviors in inflamed animals, indicating that this moleculeis a novel endogenous pain-producing substance via TRPV3 activation. According to ourco-culture experiments, FPP-evoked signals in the skin keratinocytes are relayed to theprimary sensory afferents. TRPV3 is basically a heat-activated TRP channel(thermoTRP). FPP lowered TRPV3 heat threshold leading to heightened behavioralsensitivity to noxious heat. Collectively our results suggest that FPP is a novelendogenous TRPV3 activator that causes nociception.H-17-05Leucine-rich glioma inactivated 3 (LGI3) is a neuritogenic factor actingthrough Akt and FAKWoo-Jae Park, Hyo-Soon Jeong, Hyun E Lee, Seung Hoon Lee, Su Yeon Kim, Eun-Hyun Kim, Nyoun Soo Kwon, Kwang Jin Baek, Dong-Seok Kim, Hye-Young YunDepartment of Biochemistry, College of Medicine, Chung-Ang University, Seoul, KoreaLeucine-rich glioma inactivated 3 (LGI3) is a secreted protein that belongs to theLGI/epitempin family. We previously showed that LGI3 was highly expressed in brain in atranscriptionally and developmentally regulated manner and that it regulated exocytosisthrough interaction with syntaxin 1. In this study, we found that LGI3 induced neuriteoutgrowth in Neuro-2a cells and dorsal root ganglia explants. LGI3 treatment oroverexpression increased neurite outgrowth and knockdown of LGI3 by siRNA hadopposite effect. LGI3 treatment increased phosphorylation of Akt and a 125-kDa protein.Immunoprecipitation identified the 125-kDa protein as focal adhesion kinase (FAK). LGI3overexpression increased phospho-Akt, phospho-FAK and FAK protein. Inhibition of Aktactivation by PI3 kinase inhibitor attenuated LGI3-induced FAK phosphorylation andneurite outgrowth. Taken together, we propose that LGI3 is a neuritogenic factor whosesignaling pathway involves Akt-mediated FAK activation. [Acknowledgment: KoreaResearch Foundation grant 2010-0020937]H-17-03Synthesis and degradation of synaptic proteins in the anterior cingulatecortex is required for maintaining chronic painHyoung-Gon Ko¹, Xiangyao Li³, Tao Chen³, Gi-Chul Baek¹, Min Zhuo² , ³ , *, Bong-Kiun Kaang¹ , ² , *¹National Creative Research Initiative Center for Memory, School of Biological Sciences,²Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul NationalUniversity, 599 Gwanangno, Gwanak-gu, Seoul 151-747, Korea, ³Department of Physiology, Facultyof Medicine, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, CanadaSynthesis and degradation of synaptic proteins mediated reorganization of synapticstructure, which in turn change synaptic strength. Change in synaptic strength is believedto induce pain. Here, we examined whether change of synaptic proteins in the anteriorcingulate cortex (ACC) is involved in chronic pain. To do this, we performed behavioraltests, immunoblot analysis, and electrophysiological measurements in the ACC of micesuffering from chronic pain such as neuropathic and inflammatory pain. First, we showedthat blocking of protein synthesis in the ACC decreased mechanical allodynia response inmice having chronic pain. However, infusion of protein degradation inhibitor preventsanisomycin from reducing the allodynia response. Second, we revealed that persistentpainful stimulus from periphery lead to global change of postsynaptic proteins in the ACC.Finally, blocking of protein synthesis reduce the enhanced synaptic transmission in theACC of mice having nerve injury. These results suggest that global change of synapticproteins in the ACC contributes to the chronic pain. [Supported by the National CreativeResearch Initiative Program and the World-Class University (WCU) program of theMinistry of Education, Science and Technology through the NRF in Korea]H-17-06PI3Kγis required for NMDAR-dependent long-term depression andbehavioral flexibilityJae-Ick Kim 1, 8 , Hye-Ryeon Lee 1,8 , Su-eon Sim 1,2 , Jinhee Baek 1 , Soo-Won Park 1 , Sung-Ji Ahn 6 , So Yoen Choi 7 , Yong-Seok Lee 1 , Deok-Jin Jang 1 , Kyoung-Han Kim 5 ,Kyungmin Lee 1 , Clarrisa A. Bradley 2 , Hyun Kim 7 , Eunjoon Kim 4 , Min Zhuo 2, 5 , SangJeong Kim 2,6¹National Creative Research Initiative Center for Memory, Department of Biological Sciences,College of Natural Sciences, Seoul National University, Seoul, Korea, ²Department of Brain andCognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea, ³MRCCenter for Synaptic Plasticity, School of Physiology & Pharmacology, University Walk, Bristol,BS8 1TD, United Kingdom, 4 National Creative Research Initiative Center for Synaptogenesis,Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST),Daejeon, Korea, 5 Department of Physiology, University of Toronto, Toronto, Ontario, Canada,6Department of Physiology, Seoul National University College of Medicine, Seoul, Korea,7Department of Anatomy, College of Medicine, Korea University, Seoul, Korea, 8 These authorscontributed equally to this work. *To whom correspondence should be addressed.Phosphatidylinositol 3-kinase (PI3K) has been implicated in various cellular processes,for example, cell survival, proliferation, migration, and adhesion. A growing body ofevidence has revealed the role of this kinase as a key player in synaptic plasticity andother neural functions in the brain. However, there are numerous forms of PI3K with awide variety of different functions. Importantly, the role of individual PI3K isoforms inneurons remains unknown. In this study, we examined the role of PI3Kγ, the onlymember of class IB PI3K, in hippocampal-dependent synaptic plasticity and cognitivefunctions. We found that PI3Kγis present in the hippocampus and plays a crucial andspecific role in NMDAR-mediated synaptic plasticity at SC-CA1 synapses. Genetic244 Korean Society for Biochemistry and Molecular Biology