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Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders

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Food Science and Human Wellness 2024年第5期13卷 2970-2981页

作者： Huang Zhang Lan Mo Xi Chen Mei Li Maiquan Li Yang Xu Maomao Zeng Zhiyong He Qingwu Shen Jie Chen Wei Quan College of Food Science and Technology Hunan Agricultural UniversityChangsha 410128China Henan University of Animal Husbandry and Economy Zhengzhou 450046China College of Food Science and Engineering Northwest A&F UniversityYangling 712100China State Key Laboratory of Food Science and Technology Jiangnan UniversityWuxi 214122China

Diabetes-associated cognitive dysfunction has already been attracted considerable *** glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this ***,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully *** the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for *** was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral *** details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to ***,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of ***,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free *** conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

关键词： Diabetes cognitive dysfunction N^(ε)-(carboxymethyl)lysine Neuroinflammation Metabolomic

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Developments in Biological Mechanisms and Treatments for Negative Symptoms and cognitive dysfunction of Schizophrenia

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Neuroscience Bulletin 2021年第11期37卷 1609-1624页

作者： Qiongqiong Wu Xiaoyi Wang Ying Wang Yu-Jun Long Jing-Ping Zhao Ren-Rong Wu National Clinical Research Center for Mental Disorders Department of PsychiatryThe Second Xiangya Hospital of Central South UniversityChangsha 410011China Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031China

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last *** first part of this review summarizes the pathogenesis of schizophrenia,especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and *** second part describes the novel medications and several advanced physical therapies(e.g.,transcranial magnetic stimulation and transcranial direct current stimulation)for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

关键词： Schizophrenia Genetics Epigenetics Negative symptoms cognitive dysfunction Physical therapy

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NMDA Receptor Antagonist MK801 Protects Against 1-Bromopropane-Induced cognitive dysfunction

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Neuroscience Bulletin 2019年第2期35卷 347-361页

作者： Lin Xu Xiaofei Qiu Shuo Wang Qingshan Wang Xiu-Lan Zhao School of Public Health Shandong University School of Pharmacy Liaocheng University School of Public Health Dalian Medical University

Occupational exposure to 1-bromopropane(1-BP) induces learning and memory deficits. However, no therapeutic strategies are currently available. Accumulating evidence has suggested that N-methyl-D-aspartate receptors(NMDARs) and neuroinflammation are involved in the cognitive impairments in neurodegenerative diseases. In this study we aimed to investigate whether the noncompetitive NMDAR antagonist MK801 protects against 1-BPinduced cognitive dysfunction. Male Wistar rats were administered with MK801(0.1 mg/kg) prior to 1-BP intoxication(800 mg/kg). Their cognitive performance was evaluated by the Morris water maze test. The brains of rats were dissected for biochemical, neuropathological,and immunological analyses. We found that the spatial learning and memory were significantly impaired in the1-BP group, and this was associated with neurodegeneration in both the hippocampus(especially CA1 and CA3)and cortex. Besides, the protein levels of phosphorylated NMDARs were increased after 1-BP exposure. MK801 ameliorated the 1-BP-induced cognitive impairments and degeneration of neurons in the hippocampus and ***, MK801 abrogated the 1-BP-induced disruption of excitatory and inhibitory amino-acid balance and NMDAR abnormalities. Subsequently, MK801 inhibited the microglial activation and release of pro-inflammatory cytokines in 1-BP-treated rats. Our findings, for the first time, revealed that MK801 protected against 1-BP-induced cognitive dysfunction by ameliorating NMDAR function and blocking microglial activation, which might provide a potential target for the treatment of 1-BP poisoning.

关键词： 1-Bromopropane cognitive dysfunction MK801 N-methyl-D-aspartate receptors Microglia NLRP3 inflammasome

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Promise of metformin for preventing age-related cognitive dysfunction

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Neural Regeneration Research 2022年第3期17卷 503-507页

作者： Leelavathi N.Madhu Maheedhar Kodali Ashok K.Shetty Institute for Regenerative Medicine Department of Molecular and Cellular MedicineTexas A&M University College of MedicineCollege StationTXUSA

The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's ***,competent therapies that could improve the healthspan of people have great *** of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old ***,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive ***,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal *** most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still ***,a previous animal model study implied that metformin could adversely affect cognitive function in the ***,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old *** study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the *** proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive ***,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive fun

关键词： activated microglia aging autophagy cognitive dysfunction memory metformin mTOR signaling neuroinflammation

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Death-associated protein kinase 1 is associated with cognitive dysfunction in major depressive disorder

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Neural Regeneration Research 2023年第8期18卷 1795-1801页

作者： Xiao-Hui Li Hong-Can Zhu Xue-Min Cui Wang Wang Lin Yang Li-Bo Wang Neng-Wei Hu Dong-Xiao Duan Department of Physiology and Neurobiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina

We previously showed that death-associated protein kinase 1(DAPK1)expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's *** addition,depression is a risk factor for developing Alzheimer's disease,as well as an early clinical manifestation of Alzheimer's ***,cognitive dysfunction is a distinctive feature of major depressive ***,DAPK1 may be related to cognitive dysfunction in major depressive *** this study,we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic,mild,unpredictable *** found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area,and tau was hyperphosphorylated at Thr231,Ser262,and Ser396 in these ***,DAPK1 shifted from axonal expression to overexpression on the cell *** and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive *** results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

关键词： Alzheimer's disease antidepressant drug behavioral tests cognitive dysfunction death-associated protein kinase 1 exercise hippocampus major depressive disorder phosphorylation tau protein

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Metabolic syndrome,ApoE genotype,and cognitive dysfunction in an elderly population:A single-center,case-control study

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World Journal of Clinical Cases 2021年第5期9卷 1005-1015页

作者： Jie-Yu Wang Li Zhang Jia Liu Wei Yang Li-Na Ma Department of Geriatrics Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric MedicineBeijing 100053China

BACKGROUND Metabolic syndrome(MetS)is related to poor cognitive ***,the results of previous studies were inconsistent,and whether the ApoEε4 allele modifies the association remains *** To elucidate the relationships among MetS,ApoEε4,and cognitive dysfunction in an elderly population in *** One hundred elderly patients with MetS and 102 age-and gender-matched controls were included in the *** clinical characteristics and biochemical index for glucose and lipid metabolism were *** distribution of ApoEε4 was assessed with PCR restriction fragment length polymorphism *** function was evaluated by mini-mental status examination at the 1-year follow-up *** Compared with controls,MetS patients had worse cognitive function and decreased ability to participate in activities of daily life(P=0.001 and 0.046,respectively).Patients with cognitive dysfunction had higher prevalence of MetS(62.1%vs 36.4%,Pcognitive dysfunction(Pcognitive function(time×team,Pcognitive dysfunction among an elderly population in China.

关键词： Metabolic syndrome ApoEε4 cognitive dysfunction Elderly Genotype Case-control study

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Expert Consensus on cognitive dysfunction in Diabetes

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Current Medical Science 2022年第2期42卷 286-303页

作者： Yan YANG Jia-jun ZHAO Xue-feng YU Division of Endocrinology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong UniversityJinan25000China

The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent ***,the concepts,clinical treatment,and prevention of cognitive dysfunction in patients with diabetes remain *** Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with *** on research both in China and other countries worldwide,the Expert Consensus on cognitive dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese *** consensus presents an overview,definition and classification,epidemiology and pathogenesis,risk factors,screening,diagnosis,differential diagnosis,treatment,and prevention of cognitive dysfunction in patients with diabetes.

关键词： diabetes cognitive dysfunction antidiabetic agents

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Role of GSK-3β in Isoflurane-induced Neuroinflammation and cognitive dysfunction in Aged Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第4期33卷 530-535页

作者：李世勇陈欣陈晔凌谭蕾赵以林王金韬向强罗爱林 Department of Anesthesiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Anesthesiology Wuhan Children's HospitalTongji Medical CollegeHuazhong University of Science and Technology

Summary： This study investigated the role of glycogen synthase kinase-3D （GSK-3β） in isoflu- rane-induced neuroinflammation and cognitive dysfunction in aged rats. The hippocampi were dissected from aged rats which had been intraperitoneally administered lithium chloride （LiC1, 100 mg/kg） and then exposed to 1.4% isoflurane for 6 h. The expression of GSK-313 was detected by Western blotting. The mRNA and protein expression levels of tumor necrosis factor （TNF）-a, interleukin （IL）-lβ and IL-6 were measured by real-time PCR and enzyme-linked immunosorbent assay （ELISA）, respectively. Mor- ris water maze was employed to detect spatial memory ability of rats. The results revealed that the level of GSK-3β was upregulated after isofurane exposure. Real-time PCR analysis demonstrated that isoflu- rane anesthesia increased mRNA levels of TNF-a IL-Iβ and IL-6, which was consistent with the ELISA results. However, these changes were reversed by prophylactic LiC1, a non-selective inhibitor of GSK-3β. Additionally, we discovered that LiC1 alleviated isoflurane-induced cognitive impairment in aged rats. Furthermore, the role of GSK-313 in isoflurae-induced neuroinflammation and cognitive dysfunction was associated with acetylation of NF-r,B p65 （Lys310）. In conclusion, these results suggested that GSK-3β is associated with isoflurane-induced upregulation of proinflammatory cytokines and cognitive disorder in aged rats.

关键词： isoflurane GSK-3β cognitive dysfunction neuroinflammation

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Serum neuronal pentraxin 2 is related to cognitive dysfunction and electroencephalogram slow wave/fast wave frequency ratio in epilepsy

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World Journal of Psychiatry 2023年第10期13卷 714-723页

作者： Xiao-Fen Huang Ming-Xia Xu Yue-Fan Chen Yun-Qing Lin Yuan-Xiang Lin Feng Wang Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Neurosurgery National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhou 350212Fujian ProvinceChina

BACKGROUND cognitive dysfunction in epileptic patients is a high-incidence *** mechanism is related to nervous system damage during seizures,but there is no effective diagnostic *** pentraxin 2(NPTX2)is thought to play a vital role in neurotransmission and the maintenance of synaptic *** study explored how serum NPTX2 and electroencephalogram(EEG)slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with *** To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy *** The participants of this study,conducted from January 2020 to December 2021,comprised 74 epilepsy patients with normal cognitive function(normal group),37 epilepsy patients with cognitive dysfunction[epilepsy patients with cognitive dysfunction(ECD)group]and 30 healthy people(control group).The minimental state examination(MMSE)scale was used to evaluate cognitive *** determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG *** correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE *** The serum NPTX2 level in the control group,normal group and ECD group were 240.00±35.06 pg/mL,235.80±38.01 pg/mL and 193.80±42.72 pg/mL,*** MMSE score was lowest in the ECD group among the three,while no significant difference was observed between the control and normal *** epilepsy patients with cognitive dysfunction,NPTX2 level had a positive correlation with the MMSE score(r=0.367,P=0.0253)and a negative correlation with epilepsy duration(r=−0.443,P=0.0061)and the EEG slow wave/fast wave frequency ratio value in the temporal region(r=−0.339,P=0.039).CONCLUSION Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with *** is thus a pot

关键词： Serum neuronal pentraxin 2 cognitive dysfunction Epilepsy Electroencephalogram slow wave/fast wave frequency ratio Biomarker

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Disturbance of cholinergic Grb2-associated-binding protein 1 signaling participate in the pathological process of cognitive dysfunction

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中国药理学与毒理学杂志 2017年第5期31卷 475-476页

作者： TAN Chao LU Nan-nan SHAO Ling-xiao LIU Xiu-xiu PAN Yue LIU Yi-jie YU Fang-ying LU Ying-mei 韩峰 College of Pharmaceutical Sciences Zhejiang University School of Medicine Zhejiang University City College 中国毒理学会浙江省毒理学会

OBJECTIVE A causal relationshiphas been postulated between cholinergic dysfunction and the progression of cognitive decline in neurodegenerative disorders. However,the cause of the cognitive dysfunction remains unclear. METHODS Gab1^(loxP/loxP) were bred with ChAT-Cre mice to generate ChAT-Cre; Gab1^(f/f) mice. Excitability of cholinergic neurons wererecorded using whole-cel patch clump. A series of behavioral analyses were used to address the changes of cognitive function in ChAT-Cre; Gab1^(f/f) mice. Neurochemical changes on brain of conditional knockout mice were evaluated by using immunohistochemistry and Western blotting analysis. RESULTS Grb2-associated-binding protein 1(Gab1) is adocking/scaffolding molecule known to play an important role in cell growth and survival. Here,wereport that Gab1 is decreased in cholinergic neurons in a mousemodel of AD. We found that selective downregulation of Gab1 in the septum impaired learning and memory and hippocampal long-term potentiation,whereas overexpression of Gab1 in the same area rescued the cognitive deficitsseen in ChAT-Cre; Gab1^(f/f) and APP^(swe)/PS1 mice.^(18)F-FDGmicroP ET imaging data indicated that Gab1 treatment had no effect on metabolic activity of glucose in APPswe/PS1 mice. Moreover,we identify abnormal function of SKchannelscontributes to increased firing in cholinergic neuronsof ChAT-Cre; Gab1^(f/f) mice. CONCLUSION Gab1 signaling may serve as a potential treatment target for neurological disorders involving dysfunction of central cholinergic neurons.

关键词： cholinergic neurons cognitive dysfunction Gab1 therapeutic target

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