11:10-12:00, Rm 103

NeuroscienceH-17-24Neuroprotective effect of mBHT-MC in an experimental stroke modelTae-Woo Oh¹, Hyo-Won Jung²and Yong-Ki Park¹¹Department of Herbology, College of Oriental Medicine and ²Oriental Medicine R&D Center,Dongguk University, Gyeongju 780-714, KoreaApoptosis plays an important role in neuronal death after cerebral ischemia. Recently, wereported neuroprotective properties for mBHT, a polyherbal medicine, in focalischemia/reperfusion injury induced by middle cerebral artery occlusion in rats. Thepresent study is focused on the neuroprotective effect of mBHT-methylene chloridefraction (mBHT-MC), especially anti-apoptosis in neuronal cells. mBHT-MC at 10, 25 and50 mg/kg/day was I/P administrated for 7 days after MCAO in Male Sprague-Dawley rats.We measured neurological deficit score, the infarct volume by 2,3,5-triphenyltetrazoliumchloride staining, and the expressions of Bax, Bcl-2 and caspase-3 in the ipsilateralhemisphere of the brain by western blot. We also analyzed neuronal apoptosis in theischemic brains by Nissl and Hoechst staining. I/P administration of mBHT-MC in MCAOrats significantly decreased the infarct volume, and improved neurological deficit in adose-dependent manner. The expression of caspase-3 was significantly inhibited bymBHT-MC; Bcl-2 and Bax ration was increased at the same time point. mBHT-MC alsoprevented neuronal apoptosis in ischemic brains.In conclusion, mBHT-MC has aneuroprotective effect via prevention of brain infarction and and neuronal apoptosisinduced by MCAO in rat.H-17-27BIochemical changes in AMPA receptors in the striatum by repeatedcocaine exposureHee-Jung Kim, Bong-June Yoon*Department of Biotechnology, Korea university, Seoul 136-701, KoreaProtein phosphorylation of ionotropic glutamate receptors is an importantposttranslational modification that can alter the properties of channel and can bemodulated by changing synaptic activity. Especially phosphorylation of AMPA receptorGluR1 subunit affects glutamate receptor trafficking, therefore it bears functionalsignificance for altering synaptic properties. In this study, we investigated the regulation ofAMPA receptor GluR1 subunit phosphorylation by cocaine exposure in the rat striatum invivo. Phosphorylation level at Ser845 residue of GluR1 subunit was significantly reducedin the membrane fraction of dorsomedial striatum by repeated cocaine injections. Unlikemembrane preparations, synaptic GluR1 in the dorsomedial striatum showed decrease inSer831 phosphorylation by repeated cocaine exposure. It is likely that change ofphosphorylation state of AMPA receptor in the dorsomedial striatum play a functional rolein cocaine addiction or response to cocaine exposure, such as locomotive sensitization.Non-sensitization group show generally decreased GluR1 level in synapse fractionpreparation. These data suggest that the synaptic expression of GluR1 subunit should beimportant for cocaine sensitization.H-17-25Epigenetic change of serotonin level and suceptibility to stress indepression modelJae-Won Kim and Bong-June Yoon*Department of Biotechnology, Korea University, Seoul 136-701, KoreaDepression is one of the common mental diseases, associated with both environmentaland genetic factors. Especially, early life experience is reported to cause the long-termchange of neural network, making susceptible to depression in adult. Currently, it isknown to showing depressive behavior pattern in adult when clomipramine, a kind oftricyclic antidepressant, is treated in neonatal rat. However, molecular approach to thisdepression model has not been investigated yet. In this study, we applied this depressionmodel to mice, and performed various behavior tests such as FST, OFT, and socialinteraction to measure the depressive and anxiety behavior. Also, we measured themRNA level of genes known to be involved with depression and mood-such as serotoninand orexin-in several brain regions through real-time PCR. In addition, we conductedsocial defeat stress to this model, divided stress-susceptible and resilience group, andalso conducted the same experiments to see the difference of gene expression in eachgroup.H-17-28A MAOB inhibitor induces structural changes in the medium spinyneurons of the striatum of an animal model of parkinson diseaseWon-Ju Kim¹, Mi-jung Lim²and Bong-June Yoon¹¹School of Life Sciences & Biotechnology, Korea University, Anam-Dong, Seungbuk-gu, Seoul136-701, Korea, and ²Drug Development Center, R&D Park, SK holdings, 140-1 Wonchon-dong,Yuseong-gu, Daejeon 305-712, KoreaParkinson disease is a neurodegenerative disorder of which symptoms include trouble ineffectively translating thought into voluntary movement. Parkinson disease is caused bydopamine depletion due to the loss of dopaminergic neuron in the substantia nigra. Thestructure of medium spiny neuron in the striatum, which is one of the major targets fordopaminergic neurons, is changed by dopamine depletion. MAOB inhibitor administrationis one of available treatments of the disorder to slow down the progress by reducingdopamine depletion. Here, we showed that the deficit of dopaminergic input to thestriatum caused a decrease in the number of primary neurites and dendritic spine densityon the medium spiny neurons of the dorsal striatum. A MAOB inhibitor treatment followingMPTP-treatment blocked or recovered the structural damage in a dose-dependentfashion. However, it remains to be clarified whether the MAOB inhibitor blocks (or slowsdown) the structural changes caused by MPTP or it actually induces the recovery of lostneurites or dendritic spines. [Supported by grants from SK holdings]H-17-26Functional role of glutamatergic synapses in the striatum in anxietyrelatedbehaviorYoung Lee, Won-Ju Kim, Jae-Gon Kim, Ho-Jin Lee, Bong-June Yoon*Department of Biotechnology, Korea University, Seoul 136-701, KoreaRecent findings suggest a role of the striatum in anxiety. The striatum is a critical circuitintegrator that provides processed input to cortico-striatal-thalamo-cortical (CSTC)pathway for motor control. Because the input from the basal ganglia to the thalamusmodulated by the balance between the activity of the striatonigral (direct) andstriatopallidal (indirect) pathways, the regulation of corticostriatal synapses seems to becritical for maintaining this balance. Here we examined the effect of glutamatergicsynapse in the striatum on anxiety. Mice expressing G2CT, which interfere with AMPARtrafficking in and out of synapse, show heightened anxiety in several behavioral tests.This behavior is accompanied by altered dendritic spine structures, primarily of D2Rpositiveneurons. Interestingly, localized viral expression experiments indicate that theremay be area specific regulation within the striatum of anxiety-related behavior. Our resultsshow that the alteration of glutamatergic synapses in the striatum can affect anxietyrelatedbehavior and presumably the tilted balance between striatonigral (direct) pathwayand striatopallidal (indirect) pathway underlies these behavioral abnormalities.H-17-29SIRT2 regulates HSP90 stability and α-synuclein Toxicity in oxidativestressJung Sun Min¹, Jin Chul Kim¹, Myung Ho Kor, Mi-jee Kim, Moon-gi Chae, Ji AeKim, Jeong Keun Ahn*Department of Microbiology, School of Bioscience and Biotechnology, Chungnam NationalUniversity, Daejeon 305-764, KoreaSIRT2 is a human homolog of Yeast Sir2 protein which is NAD+-dependent class IIIhistone deacetylase. SIRT2 influences a variety of cellular functions including cellprotection, cell differentiation, and cell cycle regulation. SIRT2 inhibition has beenreported to have an effect on the toxicity of α-synuclein which is a hallmark of Parkinson’s disease and interacts with HSP90. HSP90 is a molecular chaperone that regulates theprotein folding and is associated with age-related disorders. However, HSP90 regulatorymechanisms were poorly understood. We report here that HSP90 protein stability isdecreased by SIRT2 and oxidative stress. Also, SIRT2 deacetylates HSP90 andregulates the ubiquitination of HSP90. In addition, a co-chaperone of HSP90, CDC37, isdissociated from HSP90 by SIRT2 and oxidative stress. SIRT2 also affects the toxicity ofα-synuclein by regulating HSP90 which diminishes the toxicity of α-synuclein. Therefore,SIRT2-dependent HSP90 degradation in oxidative stress may be an important regulatorymechanism of age-related diseases associated with α-synuclein toxicity. For the possiblegene therapy of neurodegenerative diseases, we designed and constructed herpessimplex virus expressing SIRT2 siRNA.248 Korean Society for Biochemistry and Molecular Biology