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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi izumi Kazuko A.O'Dell Charles F.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

Fabrication of a model specimen for understanding micro-galvanic corrosion at the boundary ofα-Mg andβ-Mg17Al12

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Journal of Magnesium and Alloys 2023年第1期11卷 137-153页

作者： Zheng Shao Masashi Nishimoto izumi Muto Yu Sugawara Department of Materials Science Graduate School of EngineeringTohoku University6-6-02 Aza-AobaAramakiAoba-kuSendai 980-0579Japan

A model specimen with a single boundary of theα/βphase simulating Mg-Al alloys was successfully fabricated by spark plasma sintering.A small electrode area ofαphase orβphase was prepared using the model specimen,and the OCPs(open-circuit potentials)of each phase and a small electrode area containing theα/βphase boundary in 0.1 M NaCl at pH 8.0 were compared:theβphase exhibited a higher potential,and theαphase showed a lower potential.The OCP of the small area containing theα/βphase boundary was the intermediate value of these phases.In a small area containingα/βphase boundary,discoloration and gas bubbles were observed on theαphase,but no bubble generation was detected on theβphase.The gas bubbles were initially generated on theαphase near theβphase,but as the discoloration(corrosion)of theαphase approached theβphase,the bubbles were generated on theβphase.In micro-galvanic corrosion of theαandβphases,theβphase did not always function as the preferred cathode.Theαphase partially corroded(or discolored)and became the anodes,so that the surrounding areas were most likely to be the cathodes.When corroded areas(anodes)in theαphase approached theβphase,theβphase would become cathodes.In addition to the micro-galvanic corrosion mechanism,the role of Al in corrosion resistance at theα/βphase boundary was determined by surface analysis.

关键词： Magnesium alloy α/βphase boundary Micro-scale observation technique Micro-galvanic corrosion Spark plasma sintering

《德意志意识形态》手稿是“马克思口述、恩格斯笔录”的产物——驳黑泷正昭对大村假说的批评

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中共历史与理论研究 2024年第1期 188-213,229,230页

作者： [日]大村泉孙佳(译) 陈浩(校) 日本东北大学清华大学

黑泷正昭曾撰文批评大村假说,认为《德意志意识形态》手稿不是“马克思口述、恩格斯笔录”的产物,本文尝试对此批评展开反批评。黑泷指出,他仔细检讨了笔者对假说的证明过程,发现笔者并未能成功证明此假说。但是黑泷对其中两大关键性证... 详细信息

黑泷正昭曾撰文批评大村假说,认为《德意志意识形态》手稿不是“马克思口述、恩格斯笔录”的产物,本文尝试对此批评展开反批评。黑泷指出,他仔细检讨了笔者对假说的证明过程,发现笔者并未能成功证明此假说。但是黑泷对其中两大关键性证据的批评无法令人信服。第一大证据在于,手稿中出现了许多即时异文,这在恩格斯单独执笔的手稿中较少发现,而在马克思单独执笔的手稿中却屡见不鲜。事实上,该手稿中即时异文的出现频率是《1844年经济学哲学手稿》的两倍。为什么会发生这样的情况,黑泷对此并未加以考察。第二大证据在于,手稿中出现了许多德文同音异义词的混淆错误,笔者给出了6处例证。黑泷认为其中4处不应视为对同音异义词的替换更正,黑泷的这一看法要么以假定一份原本并不存在的手稿存在为前提,要么以否认恩格斯替换更正同音异义词这一事实为前提。因而笔者无法承认黑泷的批评是基于学术检讨做出的。

关键词：《德意志意识形态》手稿马克思口述恩格斯笔录即时异文同音异义词混淆

《德意志意识形态》是“马克思口述、恩格斯笔录”的产物吗?——对大村泉假说的考察

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中共历史与理论研究 2024年第1期 166-187,228,229页

作者： [日]黑泷正昭孙佳(译) 陈浩(校) 日本尚学院大学清华大学哲学系

针对《德意志意识形态》“费尔巴哈”章手稿的作者身份问题,大村泉在2017年提出了一种新颖而有趣的假说:虽然是恩格斯执笔写下了“费尔巴哈”章的几乎全部手稿,马克思却是手稿的真正作者,因为恩格斯只是笔录了马克思口述的内容。大村认... 详细信息

针对《德意志意识形态》“费尔巴哈”章手稿的作者身份问题,大村泉在2017年提出了一种新颖而有趣的假说:虽然是恩格斯执笔写下了“费尔巴哈”章的几乎全部手稿,马克思却是手稿的真正作者,因为恩格斯只是笔录了马克思口述的内容。大村认为证据在于手稿中出现了许多即时修改,这在恩格斯单独执笔的手稿中是从未有过的,而在马克思那里却经常发生。此外还有许多由于耳朵听错而发生的笔误。这是大村的基本证据。在仔细考察了这些证据之后,本文认为大村并未能成功证明他的假说。不过,大村假说的划时代意义在于,他第一次将马克思恩格斯1845年、1846年共同创作《德意志意识形态》手稿的过程,还原为一种动态形成过程。

关键词：马克思恩格斯《德意志意识形态》手稿 “分担问题”

Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina

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Neural Regeneration Research 2023年第5期18卷 1004-1008页

作者： Yukitoshi izumi Makoto Ishikawa Toru Nakazawa Hiroshi Kunikata Kota Sato Douglas F.Covey Charles F.Zorumski Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA Department of Ophthalmic Imaging and Information Analytics Tohoku University Graduate School of MedicineSendaiJapan Department of Ophthalmology Tohoku University Graduate School of MedicineSendaiJapan Department of Retinal Disease Control Tohoku University Graduate School of MedicineSendaiJapan Department of Advanced Ophthalmic Medicine Tohoku University Graduate School of MedicineSendaiJapan Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric conditions and results in neuronal and axonal changes that mimic glaucoma. We have used this model to determine neuroprotective mechanisms that could have therapeutic implications. In particular, we have focused on the role of both endogenous and exogenous neurosteroids in modulating the effects of acute high pressure. Endogenous allopregnanolone, a major stress-activated neurosteroid in the brain and retina, helps to prevent severe pressure-induced retinal excitotoxicity but is unable to protect against degenerative changes in ganglion cells and their axons under hyperbaric conditions. However, exogenous allopregnanolone, at a pharmacological concentration, completely preserves retinal structure and does so by combined effects on gamma-aminobutyric acid type A receptors and stimulation of the cellular process of macroautophagy. Surprisingly, the enantiomer of allopregnanolone, which is inactive at gamma-aminobutyric acid type A receptors, is equally retinoprotective and acts primarily via autophagy. Both enantiomers are also equally effective in preserving retinal structure and function in an in vivo glaucoma model. These studies in the retina have important implications for the ongoing development of allopregnanolone and other neurosteroids as therapeutics for neuropsychiatric illnesses.

关键词： allopregnanolone autophagy enantiomers excitotoxicity gamma-aminobutyric acid type A receptors glaucoma optic nerve oxysterols

Successful embolization of an intrahepatic portosystemic shunt using balloon-occluded retrograde transvenous obliteration:A case report

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World Journal of Clinical Cases 2022年第6期10卷 2023-2029页

作者： Hidemasa Saito Satoru Murata Fumie Sugihara Tatsuo Ueda Daisuke Yasui izumi Miki Hiromitsu Hayashi Shin-Ichiro Kumita Department of Radiology Nippon Medical SchoolTokyo 113-8602Japan Center for Interventional Radiology Teikyo University Chiba Medical CenterChiba 299-0011Japan

BACKGROUND A congenital intrahepatic portosystemic shunt(IPSVS)is a rare vascular abnormality that is characterized by an anomalous intrahepatic venous tract that connects the intrahepatic portal vein with the hepatic venous system.Hepatic encephalopathy is an indication for IPSVS embolization,which is technically challenging because rapid blood flow through shunts can induce the migration of embolization material to systemic veins.This case report discusses the efficacy of percutaneous balloon-occluded retrograde transvenous obliteration for treating patients with IPSVSs.CASE SUMMARY A 75-year-old woman presented with a six-month history of repeated hepatic encephalopathy due to an IPSVS without liver cirrhosis.We successfully embolized the IPSVS using percutaneous balloon-occluded retrograde transvenous obliteration with interlocking detachable coils.After the procedure,the patient exhibited no symptoms of hepatic encephalopathy for 14 mo.CONCLUSION Balloon-occluded retrograde transvenous obliteration with detachable coils can be effective for the endovascular treatment of an IPSVS.

关键词： Hepatic veins Portal vein Hepatic encephalopathy Endovascular procedures Embolization Therapeutic Case report

Reproducible reformation of a bilayer lipid membrane using microair bubbles

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液滴(英文) 2023年第3期2卷 90-98页

作者： izumi Hashimoto Toshihisa Osaki Hirotaka Sugiura Hisatoshi Mimura Sho Takamori Norihisa Miki Shoji Takeuchi Artificial Cell Membrane Systems Group Kanagawa Institute of Industrial Science and TechnologyKanagawaJapan Department of Mechanical Engineering Keio UniversityKanagawaJapan Institute of Industrial Science The University of TokyoTokyoJapan Graduate School of Information Science and Technology The University of TokyoTokyoJapan

Planar bilayer lipid membranes(BLMs)are widely used as models for cell membranes in various applications,including drug discovery and biosensors.However,the nanometer-thick bilayer structure,assembled through hydrophobic interactions of amphiphilic lipid molecules,makes such BLM systems mechanically and electrically unstable.In this study,we developed a device to reform BLMs using a microair bubble.The device consists of a double well divided by a separator with a microaperture,where a BLM was formed by infusing a lipiddispersed solvent and an aqueous droplet into each well in series.When the BLM ruptured,a microair bubble was injected from the bottom of the well to split the merged aqueous droplet at the microaperture,which resulted in the reformation of two lipid monolayers on the split droplets.By bringing the two droplets into contact,a new BLM was formed.An angled step design was introduced in the BLM device to guide the bubble and ensure the splitting of the merged droplet.We also elucidated the optimal bubble inflow rate for the reproducible BLM reformation.Using a 4-channel parallel device,we demonstrated the individual and repeatable reformation of BLMs.Our approach will aid the development of automated and arrayed BLM systems.

关键词： bubble bringing unstable

Pulsed field magnetization of multiple bulks used as field pole of a high-temperature superconducting rotating machine

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Superconductivity 2023年第1期5卷 63-68页

作者： Antomne A.Caunes Mizuki Tsuchiya Hayato Imamichi Nagisa Kawasumi Mitsuru izumi Tetsuya Ida Tokyo University of Marine Science and Technology 4-5-7KonanMinato-kuTokyo 108-8477Japan National Institute of Technology Toba College1-1Ikegami-choTobaMie 517-8501Japan

An array of three GdBa_(2)Cu_(3)O_(7‐δ)bulk high‐temperature superconductors(HTS)that mimic the field pole of a high‐power superconducting motor had been magnetized by pulsed field magnetization(PFM)while cooled by liquid nitrogen.The bulk array was magnetized by a passive PFM technique using three vortex‐type coils placed over each individual bulk and connected in series.The trapped magnetic flux density distribution was comparable to the distribution obtained with more traditional quasi‐static magnetization such as field‐cooling.This suggests that the use of PFM technique on arrays of HTS bulks is possible.PFM has also been performed using each coil individually,to magnetize each bulk sequentially.The magnetization sequences showed a maximum reduction of the peak trapped magnetic flux density of 12%due to the demagnetization effect of the magnetization sequence,while the trapped magnetization distribution was improved.

关键词： Pulsed field magnetization HTS bulk Bulk HTS field pole Multiple bulks array Large field pole Superconducting rotating machines