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F 66 ^. LÕäÕJ} $'&% Vol. 77!No. 1"Pt 2# 2015 24 1!Wjc`k@JBKIGHda) 6-OHDA lgF5 8>"/L4LhD7H(b$+ZoUN'A-0J1G ,P^Mn]Ym ±¶!EM ew%jy!¥FTK!±! Â!VLù'tE E  ¸¾²yæÜ . ( $EØQ2?+Rr|u}{yz_< 'BU(1! t[|qW%bD¢,V.!N»§9Ë'CLP(CO -6:xfie¼þvhzD.AV;7R4@V ¿,;6:" BU -ûV7R:L!xfixÐ/ OGft[|qW%bV,:gðÁC/,>¯þ ,a\kzUG¹¢Z6:" BU E LPS ãº6:t[|qW%b0PD NO á.N! IFNγ!IL-6 BAD¯þ,`YiZY~DiÄV+6 :"LPS 1i7R¯þkDë§T¹Vd~o[ï {sz?37R@!IκB DyN MyD88 oAT¹¢ D TBK1 Dy~âEãºÇ 1 ë§?¯4Q!BU E9 DkV+6B0<:"606! STAT1 Dy~âDÇ C iNOS .7RkEãºÇ 3 ë§SV6!4SV BU E+6:"4SP0P! BU E JAK1! STAT1 AT a\kzUG¹¢V+7R4@?ÌþÊVi«6! CLP CORe¼þxfiD.AV;6:@Ï.PS :"¯þ,kL$De¼þú¬Dìd%]fiE JAK1! STAT1 ¹¢?+Q!4SJ?ÅUS>2: LPS* TLR4*NFκB ¹¢kåDcYfeD¡;@ Ï.PS:" 2!fVXTG=?G6"2EL(*+ReOi'\S [_)Qp(%#& "Óç!vPs! !LB&©à·r!u¿ Pb!-V£s ó'6ÞE  v. 2 Ò×( T dÍÛÇ!?díDC/,>'¹Ü%.1¤(7R 4@1IPS>,R1!4DÜ%.1ÿdD-cw CADO-Cª7R0C=,>E÷yC5S>,B ,"dÍÛÇynpyg%aw~'ynpy@7(C OQ-cw1>(5SRêEIPS>,R"Ö$E dÍÛÇDynpy@'¹Ü%.@D¨µVP0C7 R4@VT@6>¾²VÑ<:"4SPV½Z7RC! J8ynpyCOR-cw@!EdnïÙÎK¡V ½Z6:'ðÁ 1("J:'¹%.D+ÊVOIR:L CdÍÛÇ!9S1ÚE@BRë¬V\R6:'ðÁ 2(" }~ xfi'F344!wt.160-180g!)(DEdnï[Dp ?:é =¥k¼7~CO<>dÍÛVß/6 :"ÍÛß/Ç!ynpy´@oynpy´Cy3! 4 õ§ DynpyVÑ<:"ynpyEy%egciDi{%l ~\V7R4@CO<>Ñ,![-cEy%egciD c^X?jR6:"ðÁ 1 ?EEdnïDÙÎKVnï] qüW®ãº'ICMS( ~COQW®. TZ6:" ðÁ 2 ?E bromodeoxyuridine 'BrdU(VxÐ]Y6! dÍÛÇ 2! 4! 7! 14! 28 ^ÇC¦ÆR6:" BrdU! Nestin ? 2 ø8#5S:MDV%.'¹Ü@6>!?díD D,ÜV@R6:" » ynpy´Eoynpy´CmI>!C-c1w 6! ICMS ~?Ednï:é DEV`L:" '¹Ü %.C=,>E! dÍÛÇ 2 ^OQ=6! 7 ^E @BRê1P0CB<:"!D»OQ!dÍÛÇ 3 ^0P 1 õ§CX<>Ü%.V+7Rê?!-c w@EdnïDÙÎKCADO-B³1°HD0½Z 6!9D¹C=,>|Ô7R" 3!ER stress inhibits synaptic plasticity in the olfactory bulb underlying aversive olfactory learning # 1 !BVh 1 !Hza 1! 2 ô) 1 ' 1 ÓI E  v. Ò×! 2 ÓIE  vJ¦È Ò×( Tunicamycin (TM) induces endoplasmic reticulum (ER) stress in the lumen, which is linked to neuronal death in neurodegenerative diseases. Aversive olfactory learning was prevented by intrabulbar infusion of TM. Using elec- trophysiology, we revealed TM has an inhibitory effect on the late phase of long-term potentiation induced at dendro- dendritic synapses in the olfactory bulb. These results sug- gest that ER stress impaired olfactory learning by inhibit- ing synaptic plasticity in the olfactory bulb. 4!<H,9I:GL(*+A-0J1G,) LPS lg P^Mn])C.;3B 4!6!&*! Â!VLù 'tE E  ¸¾²yæÜ. ( '¹{,î¤?E!mzXj{ky~'NA[,'¹ Ü57R1lD{,MC¿PSR"NA E! MG ,V+7R@,US>/Q!1lD{,C OR NA DÃý1{,î¤C/3R'¹Üè>(C= B1R@5SR" NA D MG ¢,+ßE!ñCXj{ ky~ β2 òCV6:ß;@ÅUS!ðÝ! β2 òC X_lciDgzrdy~EÀMBtY[|\yX¢,

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Page 1: nsg01-13/ky449270409900053617physiology.jp/wp-content/uploads/2015/01/0770100024-pt2.pdf · the bilateral common carotid artery for 5min. YKS was ad-ministered to the animals

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3�ER stress inhibits synaptic plasticity in the olfactorybulb underlying aversive olfactory learningÌ Æ 1C�uv 1Íwxy 12Î Ïz 1�1�P����>�����2�P����>�¶ÐÑ��� Tunicamycin (TM) induces endoplasmic reticulum (ER)

stress in the lumen, which is linked to neuronal death inneurodegenerative diseases. Aversive olfactory learningwas prevented by intrabulbar infusion of TM. Using elec-trophysiology, we revealed TM has an inhibitory effect onthe late phase of long-term potentiation induced at dendro-dendritic synapses in the olfactory bulb. These results sug-gest that ER stress impaired olfactory learning by inhibit-ing synaptic plasticity in the olfactory bulb.

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allose���� �� TXNIP���� GLUT1���������������� �!� D-glucose�"�#$%&�'(�)*+��,-. /0�123.�45� p27kip16�7� ��8 9:;<=>?@A��B��� ��8� 9C1�DEFBG?H/0�1I

8��������� Fyn���������������������JK� 1�� L 2�M �N 2�OPQR 2����� 2�ST�� 2�U� V 2W1XY��Z��Z�[ 4���2XY����\Z�]^_[��2� N9`�aRhobc�d��C1ef�eghij�kPE� �

k!l �"#�9`�mB��n$F%o�(���B1Ipq�rsE�t� ROKu&�vw�xc+ N?�� Fynyz��bc�d�{��I 0��2�|z}~��e���Fyn.��7������$ Fyn?'�'�C1�Fyn�&�vw N?���b����{���I�^_DE�(�� ��)B�� �"#�m�1�b�����m��b����Fyn*��)��$���B��+��I���,-|�=���./�)B���b���? Fyn�����c�f01� N�*��)�����?t����� FynE�b���� N23��$'���4��� FynE'��.5G�IRNA ¡�1�b����¢£����E� �"#�67�8¤��It�8¤E�¢£�����¥�¦9�b����§�C1?�eb�� ��I����b���� N23� Fyn'��¨�©ª���� �"#.67� 9 ��Ipu�'(���b���E�Fyn�&�vw�xc+ N?���«� N23�mB���7 �� Fyn?'�C1t?���� �"#�9`C1t?.¬­ ��I

9�Neuroprotective effect of yokukansan in the acutephase of experimental ischemic strokeY. Liu�T. Nakamura�T. Toyoshima�T. Yamamoto�T. ItanoWDepartment of Molecular Neurobiology, KagawaUniversity Faculty of MedicineaOur previous study demonstrated the traditional herbalmedicine yokukansan (YKS) has preventive effect onischemic dementia induced by cerebral ischemia�reperfu-sion injury in gerbils. The present study investigates theneuroprotective effect of YKS in the acute phase of experi-

mental ischemic stroke with therapeutic time window andunderlying mechanism.Transient forebrain ischemia was induced by occludingthe bilateral common carotid artery for 5min. YKS was ad-ministered to the animals 30min before and 3h after ische-mia and then daily (300mg�kg). We examined neuronaldeath, inflammatory reaction, oxidative stress in the hip-pocampus 72h after ischemia�reperfusion injury, and in-vestigated functional deficits.YKS treatment significantly reduced hippocampal neu-ronal loss, decreased the number of Iba1 (microgliamarker) also 8-OHdG (a marker of oxidative stress) posi-tive cells and 72h after brain ischemia, inhibited ischemia-induced the level of TNF-α and HEL. YKS treatment alsoreduced the locomotor activity deficit 72h after ischemiaand improved memory impairment.In conclusion, these findings suggest that YKS treat-ment has antioxidant propertied resulting in the suppres-sion of oxidative DNA damage and lipid peroxidation, aswell as anti-inflammatory effects of YKS resulting in re-duction of microglial activation and leukocyte infiltrationleading to reduced neuronal death and enhancing func-tional recover in ischemia�reperfusion injury. Our resultsare considered important for extension of the therapeutictime window of YKS treatment in acute cerebral ischemia,which might be a potential candidate for the treatment ofhuman stroke.

10�� !"�# RAW264.7$%&'()"*+ LPS,-./012� NF-κB�3456789�:;<=>?@AB6C9:®¯� 1�T°;� 2�<Y=± 1�²�>³ 1W1S?��Z��´µ9`�¶·�2��Z[����\Z�^_[��@`�¶·a¸AB¹���)e}��d8¤ºD»1¼*½¾+E��C¿Ày+���WAChaDE��Á Â�FÃÄÅÆ�G���7�ÇÈÉtCIrsEt��D��ÊËÌÍ�1Î�ÊH¦�Ï+Ð�e�mB��¼*½¾+.ÑÒ�ÓÔÕ¤� 9C1t?��ÊIJ�1ÖK�e��L%C1t?�70G���I�^_DE�¼*½¾+�×ÑÒ�)� N2Ø�7�AB?���CMÙWlipopolysaccharide�LPSaÚÛ�1Ð�zgh�¾�ÑÒNÜ�OC1¼*½¾+�Ý(��+��I¸�/¹RAW264.7Ð�eÐ�zgh�¾ ��mB��LPSÚÛ��ÑÒNÜ�ÞÉ�� �Cß�m�1ÑÒ

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����� ��� ������ κB�nuclearfactor-kappa B�NF-κB��������������� �!"#$�%&'(&�LPS���)��*�������� �!"�+,�-.�/�0)�1��2��3456$�#78&'9:";���� <�LPS=>�?@��AB� TNF-

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%�UK�PVO¥=>�ICMS�W#$45��Q�X�Y¦#1�0�78&'��Q�X�Y¦�+45�£¤=§�< CFAZ¨<£¤�?@©ª«4�[\%5+@�Rostral ForelimbArea�RFA��]�¬�Z¨6^_��­®U�OB&'(&�]+?G¬�Z¨U£¤§ 1`¯epa��S�����%�RFAZ¨<�S°¯�#b%5©ª±c�² e

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13�Geniculocortical projections in the visual cortexwith the duplicated retinotopic map induced by monocu-lar enucleationK. Kameyama�Y. Tsuchie�H. Miyata�Y. Hata�Divi-

sion of Integrative Bioscience, Tottori University GraduateSchool of Medical Sciences�

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Visual input is received by retinal ganglion cells andtheir axons project mainly to the lateral geniculate nucleus(LGN) of the thalamus. Then neurons in the LGN sendtheir axons to the primary visual cortex (V1). Precise pro-jections of the retinogeniculate and geniculocortical path-ways render the topographic arrangement called retino-topy in the visual cortex. During the developing stage,both molecular guidance and neural activity are thoughtto play an important role in the formation of the retino-topic map, although the precise mechanism is still un-known.A previous electrophysiological study using hamstersreported that monocular enucleation in early postnataldays induces a disarrangement of the retinotopic map inV1, resulting in the duplication of the central visual field.We used an optical imaging technique to investigate thechange of the retinotopic map more precisely in the mo-nocularly enucleated (ME) animals. We observed the dupli-cation of the retinotopic map clearly across V1 which is ip-silateral to the intact eye. The responding cortical area inthe ME animals was larger compared with the ipsilateraleye region of normal animals. This functional change mayreflect a reorganization of the neural connections. Here, wefocused on the geniculocortical pathway which is the pri-mary afferent input to V1. To examine possible changes inthe geniculocortical projections, we injected neural tracersinto the LGN. We visualized the geniculocortical afferentsin V1 and compared their location in V1 with the retino-topic map. The results suggest that the functional changeof retinotopy is presumably accompanied with an anatomi-cal alteration of the visual pathways.This work was supported by JSPS KAKENHI GrantNumber 25830013.

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17���� !�"#�$%&'�(��)2Cl-C.OXT-A*COA-Cl+�,-./01F. Lu1�N. Okabe1�N. Himi1�E. Nakamura-Maruyama1�

T. Shiromoto1� K. Narita1� I. Tsukamoto2� T.Maruyama2�N. Sakakibara3�O. Miyamoto1� 1Physiology2, Kawasaki Medical School�2Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa Univer-sity� 3Kagawa School of Phamaceutical Sciences,Tokushima Bunri University#2Cl-C.OXT-A (COA-Cl) is a novel synthesized adenosineanalogue with the molecular weight of 284. It is soluble,stable and easy to synthesize. It has been reported thatCOA-Cl exerts a strong angiogenetic activity in humanumbilical endothelial cells (HUVEC). Our previous studyshowed the neuroprotective effects of COA-Cl on ischemiastroke that it reduced infarct volume, inhibited apoptotic

cell death and attenuated the neurological deficits. Thepurpose of our present study is to evaluate the neuropro-tective effects of COA-Cl on intracerebral hemorrhage(ICH), another common type of stroke, and investigate thepotential mechanism of action. Sprague-Dawley (SD) ratswere used for this study. ICH models were performed bythe injection of 100μl autologous blood from femoral arteryinto the right basal ganglia. COA-Cl (30μg�kg) was in-jected intracerebroventricularly 10min after ICH. A bat-tery of behavioral tests, including body swing test, fore-limb placing test and corner turn test, were performed toexamine sensorimotor deficits with a time course as 1d, 3dand 7d after ICH. To understand the potential mechanismof how COA-Cl work at the acute phase of ICH, we exam-ined brain edema 1day after ICH using water content test,and evaluated the anti-apoptosis role of COA-Cl. Oxidativestress, a primary cause for the edema formation, was alsoexamined by a DNA oxidative marker (8-OHdG). Our re-sults showed that the rats in COA-Cl group significantlyattenuates the sensorimotor deficits and reduces brainedema compared with ICH ones. By immunohistochemis-try method, we found that both TUNEL positive cells and8-OHdG positive cells were fewer around the hematoma ofCOA-Cl treated rats compared with ICH ones. These re-sults indicated that COA-Cl may have neuroprotective ef-fects on ICH that it reduces brain edema, inhibits neuronalloss and improves ICH-induced motor deficits. Further-more, we provide the first evidence that COA-Cl may havean anti-oxidative role, which may be one of the potentialmechanisms for its neuroprotective effects on the acutephase of ICH.

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32�Rare sugar D-psicose prevents progression anddevelopment of diabetes in Type 2 Diabetes Mellitusmodel Otsuka-Long-Evans-Tokushima Fatty (OLETF) ratsA. Hossain1�2�L. Sui1�F. Yamaguchi1�K. Kamitori1�Y.Dong1�I. Tsukamoto1�T. Iida2�M. Tokuda1 1Cell Physi-

ology, Faculty of Medicine, Kagawa University, Kagawa,Japan�2Research Institute, Matsutani Chemical IndustryCo. Ltd., Hyogo, Japan�Background: Prevalence of global obesity has emerged

as the single most life-style-related health problem, mostlydue to excess calorie leading to one of its complications, in-sulin resistance followed by concomitant increase ofT2DM. To cope with the increased demand of insulin pan-creatic β-cells become over active and in turn hy-pertrophic and injured, leading to β-cell failure followed byglucose intolerance. This circumstance demands age-adjusted balanced food intake in obese-tendency subjects.Objectives: We introduce a zero-calorie sweet-taste foodadditive, D-psicose, a rare sugar produced in Kagawa Uni-versity, which has been evaluated as a unique metabolicregulator against hyperglycemia and hyperlipidemia, andthus represents as a safe and non-toxic compound to main-tain blood glucose levels through the preservation of pan-creatic β-cells in OLETF rats.Methods: Treated OLETF rats were fed 5ß D-psicosein drinking water for 60 weeks. Control OLETF and non-diabetic control, LETO rats were fed water only. Bodyweight, food and drink intake were measured weekly, andblood glucose and insulin monthly. Serum was collected forbiochemical analysis. Oral glucose tolerance test was per-formed. Liver, pancreas and other organs were preservedand stained as per need.Results: D-psicose significantly controlled abdominal fataccumulation and thus prevented excess body weight in-crease. D-psicose improved insulin resistance through con-stant maintenance of blood sugar levels. Oral glucose toler-ance test showed reduced blood glucose levels suggestingalso the improvement of insulin resistance. D-Psicose sig-nificantly attenuated progressive β-islet fibrosis and pre-served islets, evaluated by hematoxylin-eosin staining,Masson�s trichrome staining and immunostainings of insu-lin and α-smooth muscle actin.Serum levels of proinflammatory and anti-inflammatoryadipocytokines were also controlled well by D-psicosetreatment.Conclusions: Rare sugar D-psicose might be a promisingstrategy for the prevention of obesity, maintenance ofblood sugar, and preservation of pancreas β-cells.