Deletion of N-myc downstream-regulated gene 2 attenuates reactive astrogliosis and inflammatory response in a mouse model of cortical stab injury

N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the CNS. In this study, we examined the expression and the role of Ndrg2 after cortical stab injury. We observed that Ndrg2 expression was elevated in astrocytes surrounding the wounded area as early as day 1 after injury in wild-type mice. Deletion of Ndrg2 resulted in lower induction of reactive astroglial and microglial markers in the injured cortex. Histological analysis showed reduced levels of hypertrophic changes in astrocytes, accumulation of microglia, and neuronal death in Ndrg2-/- mice after injury. Furthermore, activation of the IL-6/signal transducer and activator of transcription 3 (STAT3) pathway, including the expression of IL-6 family cytokines and phosphorylation of STAT3, was markedly reduced in Ndrg2-/- mice after injury. In a culture system, both of Il6 and Gfap were up-regulated in wild-type astrocytes treated with forskolin. Deletion of Ndrg2 attenuated induction of these genes, but did not alter proliferation or migration of astrocytes. Adenovirus-mediated reexpression of Ndrg2 rescued the reduction of IL-6 expression after forskolin stimulation. These findings suggest that Ndrg2 plays a key role in reactive astrogliosis after cortical stab injury through a mechanism involving the positive regulation of IL-6/STAT3 signaling. © 2014 International Society for Neurochemistry

上部消化管出血における血液凝固第XIII因子活性の低下

We report on blood coagulation factor XⅢ（F１３）activity in upper gastrointestinal bleeding （UGIB）due to peptic ulcer（PU）. 【Methods】From January ２０１１ to December ２０１６, 42 patients who had UGIB with PU, performed endoscopic hemostasis（EH）, and measured F１３ activity （normal range：７０‐１４０％）, were retrospectively studied. The clinical signs, peripheral blood, biochemistry, coagulation, F１３ activity, and endoscopic findings were examined by logistic regression analysis（LRA）in３２patients with successful hemostasis and１０patients with rebleeding. 【Results】There were２５elderly patients aged７０ and over. The average F１３ activity was ６５．７±２２．５％, ６８．３±２２．１％ in the case of successful hemostasis, below the lower limit of normal, and further decreased to ５７．５±１８．１％ in the case of rebleeding. LRA showed association with rebleeding in Forrest classification and F１３activity. 【Conclusion】F１３activity decreased in many cases of UGIB due to PU, and associated with rebleeding after EH

The effect of Ndrg2 expression on astroglial activation

N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the central nervous system (CNS). To study the expression and possible role of Ndrg2 in quiescent and activated astrocytes, mice were administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP), a Parkinson disease (PD)-related neurotoxin which causes both neurodegeneration and glial activation. Immunohistological analysis revealed that Ndrg2 was highly expressed in both types of astrocytes, but less so in astrocytes during the early process of activation. Ndrg2 was also expressed in astrocyte-like cells, but not in neurons, in human brains from PD and Cortico-basal degeneration (CBD) patients. In cultured astrocytes, gene silencing of Ndrg2 significantly enhanced the numbers of 5-bromo-2′-deoxy-uridine (BrdU)-incorporated and proliferating cell nuclear antigen (PCNA)-positive cells, and reduced the length of cell processes and the amount of F-actin. In contrast, adenovirus-mediated overexpression of Ndrg2 significantly reduced the numbers of BrdU-incorporated and PCNA-positive cells, and enhanced the amount of F-actin. Fractionation and immunocytochemical analysis further revealed that Ndrg2 was located in different cellular fractions including the cytosol and cell surface membranes. These results suggest that Ndrg2 may regulate astroglial activation through the suppression of cell proliferation and stabilization of cell morphology. © 2011 Elsevier Ltd. All rights reserved

A study of transileocolic vein obliteration (TIO) for gastric varices

Seven cases of giant gastric varices were treated using TIO combined with balloon occlusion of the gastro-renal shunt, for the purpose of reviewing the significance of TIO in the treatment of gastric varices. In 6 of the 7 cases, giant varices were cured completely. In the unsuccessful case, it was a giant varix (the minimum diameter was 25 mm or more) which had been failed to be treated by the TIO. In 3 of the 7 cases, the varices on the gastric fornix had ruptured ; therefore, emergency TIO was undertaken and resulted in successful hemostasis and disappearance of the varices. After treatment using this technique, one case developed esophageal varices, and two patients showed a reduction in esophageal varices. In case where gastric varices had been accompanied by RC sign-positive esophageal varices, favorable results were obtained with obliteration of the gastro-renal shunt was combined with compression of the esophagus which had served as another shunt in these cases. After TIO, hepatic function remained unchanged or improved slightly. No case showed exacerbation of hepatic function. For massive gastric varices with an inside diameter of up to 2 cm, transileocolic vein obliteration (TIO) combined with balloon occlusion of the gastro-renal shunt, which occludes the shunt in an anterograde manner, secures the occlusion of the shunt with no complications. This technique seems to be an effective therapy for gastric varices

Putative Neural Network Within an Olfactory Sensory Unit for Nestmate and Non-nestmate Discrimination in the Japanese Carpenter Ant: The Ultra-structures and Mathematical Simulation

Ants are known to use a colony-specific blend of cuticular hydrocarbons (CHCs) as a pheromone to discriminate between nestmates and non-nestmates and the CHCs were sensed in the basiconic type of antennal sensilla (S. basiconica). To investigate the functional design of this type of antennal sensilla, we observed the ultra-structures at 2D and 3D in the Japanese carpenter ant, Camponotus japonicus, using a serial block-face scanning electron microscope (SBF-SEM), and conventional and high-voltage transmission electron microscopes. Based on the serial images of 352 cross sections of SBF-SEM, we reconstructed a 3D model of the sensillum revealing that each S. basiconica houses > 100 unbranched dendritic processes, which extend from the same number of olfactory receptor neurons (ORNs). The dendritic processes had characteristic beaded-structures and formed a twisted bundle within the sensillum. At the “beads,” the cell membranes of the processes were closely adjacent in the interdigitated profiles, suggesting functional interactions via gap junctions (GJs). Immunohistochemistry with anti-innexin (invertebrate GJ protein) antisera revealed positive labeling in the antennae of C. japonicus. Innexin 3, one of the five antennal innexin subtypes, was detected as a dotted signal within the S. basiconica as a sensory organ for nestmate recognition. These morphological results suggest that ORNs form an electrical network via GJs between dendritic processes. We were unable to functionally certify the electric connections in an olfactory sensory unit comprising such multiple ORNs; however, with the aid of simulation of a mathematical model, we examined the putative function of this novel chemosensory information network, which possibly contributes to the distinct discrimination of colony-specific blends of CHCs or other odor detection

神経細胞障害と細胞ストレスに着目した覚醒剤少量投与による実験動物モデルの解析

覚醒剤の少量反復投与により、神経細胞障害や酸化ストレスといった覚醒剤の多量投与により引き起こされる反応の有意な変化が観察されず、小胞体ストレスのマーカーであるGRP78(抗KDEL抗体)が有意に増加するこれまでの覚醒剤投与モデル動物とは異なる病態を示す実験動物モデルを作成した。このモデル動物を解析することにより、覚醒剤濫用における病態解明に有用な情報を得ることが出来ると考えられ、現在解析中である。This study examined the effect of repeated administration of methamphetamine (METH) on endoplasmic reticulum stress (ERS) in the dopaminergic neurons of rats. Lower doses of METH (0.5 and 1.0 mg/kg/day for 5d) increased GRP78 (KDEL), one of ERS markers, although superoxide dismutase-1, but no GRP78, was increased at higher doses (5 and 10 mg/kg/day for 5d). Further studies on ERS in METH-treated rats could contribute the understanding of the pathophysiology of METH-induced neuronal damages.研究課題/領域番号:20790466, 研究期間(年度):2008-200

Bulletin de l'Association française pour l'étude du quaternaire, vol. 8, n°4, 1971.

金沢大学医薬保健研究域医学系少量の覚せい剤を反復投与した動物を濫用初期モデル動物とした。このモデル動物に10 mg/kgの覚せい剤を投与後の中脳および線条体の細胞ストレス、神経細胞および神経活動のマーカー蛋白の変化を解析した。その結果、中脳では、抑制性神経のGABA作動性神経のマーカー(GAD67)の有意な増加を認め、線条体では小胞体ストレスマーカーおよびGAD67だけでなく、興奮性神経のグルタミン酸作動性神経のマーカーと、神経活動の指標となるc-fosの有意な増加を認めた。以上の結果より我々のモデル動物では、黒質線条体路だけでなく線条体視床路にも影響し、線条体の神経細胞の易活性化が惹起されていることが示唆された。The effects of administering low-dose Methamphetamine (METH) prior to the administration of high-dose METH on the neural activity of rats were examined. The rats were administered a low dose of METH or saline for 5 consecutive days (m5 and s5 groups), followed by a high dose of METH on Day 6 (m5M and s5M groups). Markers of neuronal cells, such as vesicular glutamate transporter 2 (VGLUT) in the striatum and glutamate decarboxylase 67 (GAD67) in the midbrain and striatum, were analyzed by western blotting. The expression of c-fos, a marker of neural activity, in the striatum was analyzed using immunohistochemistry. The expression levels of VGLUT and GAD67 were significantly higher in the m5M than in the s5M group. The numbers of c-fos-positive cells were significantly higher in m5M than in the other groups. These results suggest that preadministration of low-dose METH prior to high-dose METH administration in rats may alter thalamostriatal pathway as well as nigrostriatal pathway.研究課題/領域番号:15K08888, 研究期間(年度):2015-04-01 - 2018-03-3