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A distinct pattern of memory and attention deficiency in patients with depression

Chinese Medical Journal 2013年第6期126卷 1144-1149页

作者： LUO Lan-lan CHEN Xin CHAI Yan LI Jin-hong HANG Mian ZHANG Jian-ning Department of Psychology Tianjin Huanhu Hospital Tianjin 300060 China Department of Neurosurgery Tianjin Neurological InstituteTianjin Medical University General Hospital Tianjin 300052China

Background Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinctpattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Me^ods Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression （HAMD17scale）The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2＆7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine （75-300 mg/d）, Fluoxetine （20-40 mg/d）, Paroxetine （20-40 rag/d）, and Sertraline （50-150 mg/d）. After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2＆7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. Results The memory quotient （MQ） was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2＆7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory （DM）, free recall （FR）, associative learning （AL）, and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Conclusions Depressive patients suffer from short-term memory deficits, and attention ex

关键词： cognitive deficits anti-depressive drugs depression attention memory

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Tissue-resident memory-like ILCs: innate counterparts of TRM cells

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Protein & Cell 2020年第2期11卷 85-96页

作者： Xianwei Wang Zhigang Tian Hui Peng The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Division of Molecular Medicine Hefei National Laboratory for Physical Sciences at MicroscaleThe CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Life SciencesUniversity of Science and Technology of ChinaHefei 230027China Institue of Immunology University of Science and Technology of ChinaHefei 230027China

Innate lymphoid cells(ILCs)are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors;however,recent studies have revealed the adaptive features of ILCs.Mouse cytomegalovirus(MCMV)-and cytokine-induced memory natural killer(NK)cells circulate in the blood and are referred to as conventional memory NK cells.In contrast,virusand hapten-induced memory NK cells,hapten-induced memory ILC1s,and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung,and are referred to as tissue-resident memory ILCs.Considering their similar migration patterns and memory potential,tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T(T r m)cells.Both tissue-resident memory ILCs and TRM cells share common characteristics in terms of dynamics,phenotype,and molecular regulation.The emergence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression.This review discusses the evidence supporting tissue-resident memory NK cells and other memory ILC subsets,compares them with TRM cells,and highlights key unsolved questions in this emerging field.

关键词： tissue-residency innate lymphoid cells immunological memory TRM cells

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A high methionine,low folate and vitamin B_6/B_(12) containing diet can be associated with memory loss by epigenetic silencing of netrin-1

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Neural Regeneration Research 2019年第7期14卷 1247-1254页

作者： Anuradha Kalani Pankaj Chaturvedi Komal Kalani Pradip K.Kamat Poonam Chaturvedi Neetu Tyagi Department of Physiology School of MedicineUniversity of Louisville Medicinal Chemistry Department CSIR-Central Institute of Medicinal and Aromatic Plants Pharmacology Department and Toxicology Higuchi Biosciences CenterUniversity of Kansas Department of Neurology Dr.Ram Manohar Lohia Institute of Medical Sciences

memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.

关键词： Alzheimer’s disease epigenetics memory methionine 5-methylcytosine methylation netrin-1

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Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the hippocampus of chronic multiple-stressed rats

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Chinese Medical Journal 2006年第2期119卷 140-147页

作者： SUN Chen-you QI Shuang-shuang LOU Xin-fa SUN Shu-hong WANG Xin DAI Kai-yu HU Si-wang LIU Neng-bao Department of Anatomy Wenzhou Medical College Wenzhou 325035 China Pharmaceutical Department Second Affiliated Hospital of Wenzhou Medical College Wenzhou 325027 China Department of Histology and Embryology Tongji Medical School Huazhong University of Science and Technology Wuhan 430030 China

Background The effect of chronic stress on cognitive functions has been one of the hot topic in neuroscience. But there has been much controversy over its mechanism. Such single stressor applied in the past could not simulate complicated living circumstances that people confronted with. The aim of this study was to investigate the effects of chronic multiple-stress on learning and memory as well as on the levels of calcium/calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）, calmodulin （CAM） mRNA, and cAMP-response element binding protein （CREB） mRNA in the hippocampus of rats. Methods The rats were divided randomly into stressed and control groups. The stressed group was given chronic multiple-stress for 6 weeks to set up a chronic multiple-stressed model. The rats＇ performance of spatial learning and memory was tested using Morris Water Maze （MWM） and Y-maze. Meanwhile, the expressions of CAMKII, CAM mRNA and CREB mRNA of rats＇ hippocampus were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction （RT-PCR）, respectively. In addition, the width of synaptic cleft and the thickness of post-synaptic densities （PSD） were observed in the hippocampal CA3 region of rats by electron microscopy. Results After exposure to chronic multiple-stress for 6 weeks, the ability of learning and memory of the stressed group was higher than that of the control group （P〈0.05, P〈0.01）. The width of synaptic cleft was smaller and the thickness of PSD was larger in the hippocampal CA3 region of the stressed group than in that of the control group （P〈0.01）. The CAMKII immunostaining of the stressed group was stronger than that of the control group in the stratum radiatum and oriens of the hippocampal CA1 and CA3, especially in the stratum oriens. Quantitative analysis indicated that the expression of CAMKII, CAM mRNA, and CREB mRNA in the hippocampus of the stressed group was higher than that of the control group （P〈0.05, P〈0.01）. Conclusions The capacity of learning and memory can be enhanced after

关键词： learning memory calcium/calmodulin-dependent protein kinase Ⅱ calmodulin mRNA cAMP-response element binding protein mRNA

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Human CD4 ＋ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

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Cellular & Molecular Immunology 2013年第3期10卷 261-274页

作者： Gabriela Gonzalez-Perez Norma C Segovia Amaranta Rivas-Carvalho Diana P Reyes Honorio Torres-Aguilar Sergio R Aguilar-Ruiz Claudine Irles Gloria Soldevila Carmen Sainchez-Torres 1Department of Molecular Biomedicine Centre de Investigacion y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN) Mexico City Mexico Department of Physiology Facultad de Medicina Mexico City Mexico Department of Immunology Institute de Investigaciones Biomedicas Universidad Nacional Autonoma de Mexico (UNAM) Mexico City Mexico

The peripheral repertoire of CD4＋ T lymphocytes contains autoreactive cells that remain tolerant through several mechanisms. However, nonspecific CD4＋ T cells can be activated in physiological conditions as in the course of an ongoing immune response, and their outcome is not yet fully understood. Here, we investigate the fate of human naive CD4＋ lymphocytes activated by dendritic cells （DCs） presenting endogenous self-peptides in comparison with lymphocytes involved in alloresponses. We generated memory cells （Tmem） from primary effectors activated with mature autologous DCs plus interleukin （IL）-2 （Tmauto）, simulating the circumstances of an active immune response, or allogeneic DCs （Tmallo）. Tmem were generated from effector cells that were rested in the absence of antigenic stimuli, with or without IL-7. Tmem were less activated than effectors （demonstrated by CD25 downregulation） particularly with IL-7, suggesting that this cytokine may favour the transition to quiescence. Tmauto and TmaHo showed an effector memory phenotype, and responded similarly to polyclonal and antigen-specific stimuli. Biochemically, IL-7-treated Tma^o were closely related to conventional memory lymphocytes based on Erk-l/2 activation, whereas Tmauto were more similar to effectors. Autologous effectors exhibited lower responses to IL-7 than allogeneic cells, which were reflected in their reduced proliferation and higher cell death. This was not related to IL-7 receptor expression but rather to signalling deficiencies, according to STAT5 activation These results suggest that ineffective responses to IL-7 could impair the transition to memory cells of naive CD4＋ T lymphocytes recognizing self-peptides in the setting of strong costimulation.

关键词： human CD4＋ T cells IL-7 memory self-peptides

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Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress

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Neuroscience Bulletin 2013年第6期29卷 737-744页

作者： Xiu-Ping Sun Si-Di Li Zhe Shi Teng-Fei Li Rui-Le Pan Qi Chang Chuan Qin Xin-Min Liu Research Center of Pharmacology and Toxicology Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical College Institute of Laboratory Animal Sciences Chinese Academy of Medical Sciences and Peking Union Medical College

Shen Yuan Gan（SYG） is a Chinese herbal prescription composed of total saponins of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia（2：1）.Our previous studies have demonstrated that SYG has antidepressant-like effects in various mouse models of behavioral depression.The present study aimed to test whether SYG affected chronic mild stress（CMS）-induced depression and cognitive impairment in mice.We found that a 5-week CMS schedule induced significant degradation of the coat state,decreased sucrose intake in the sucrose-preference test,and increased the latency to feed in the noveltysuppressed feeding test.All of these CMS-induced changes were ameliorated by SYG（100 and 200 mg/kg） and fluoxetine（10 mg/kg）.In addition,SYG restored the decreased monoamine neurotransmitter concentrations（serotonin,dopamine,norepinephrine and acetylcholine） induced by CMS in the prefrontal cortex.Interestingly,SYG ameliorated CMS-induced cognitive impairment in the step-through test,and increased the acetylcholine level in the prefrontal cortex.These results suggest that SYG has an antidepressant-like action and enhances cognition by modulating the serotonin,dopamine,norepinephrine,and acetylcholine levels in the prefrontal cortex.

关键词： mice antidepressant neurotransmitter memory Panax ginseng Polygala tenuifolia

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Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity

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Cellular & Molecular Immunology 2021年第7期18卷 1761-1771页

作者： Nina Dumauthioz Benjamin Tschumi Mathias Wenes Bastien Marti Haiping Wang Fabien Franco Wenhui Li Isabel CLopez-Mejia Lluis Fajas Ping-Chih Ho Alena Donda Pedro Romero Lianjun Zhang Translational Tumor Immunology Group Ludwig Cancer ResearchUniversity of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Ludwig Cancer Research Institute Lausanne BranchEpalingesSwitzerland Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College100005BeijingChina Suzhou Institute of Systems Medicine SuzhouJiangsu215123China Center for Integrative Genomics University of LausanneLausanneSwitzerland

memory CD8 T cells can provide long-term protection against tumors,which depends on their enhanced proliferative capacity,self-renewal and unique metabolic rewiring to sustain cellular fitness.Specifically,memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands.In contrast,tumor-infiltrating lymphocytes(TILs)display severe metabolic defects,which may underlie their functional decline.Here,we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),the master regulator of mitochondrial biogenesis(MB),favors CD8 T cell central memory formation rather than resident memory generation.PGC-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide vaccination.Importantly,CD8 T cells with enhanced PGC-1αexpression provide stronger antitumor immunity in a mouse melanoma model.Moreover,TILs overexpressing PGC-1αmaintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free host.Altogether,our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation,metabolic fitness,and antitumor immunity in vivo.

关键词： PGC-1α Mitochondria CD8 memory Anti-tumor immunity

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Effects of the Hydro-Alcoholic Extract of Nigella Sativa on Scopolamine-Induced Spatial memory Impairment in Rats and Its Possible Mechanism

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Chinese Journal of Integrative Medicine 2015年第6期21卷 438-444页

作者： Mahmoud Hosseini Toktam Mohammadpour Reza Karami Ziba Rajaei Hamid Reza Sadeghnia Mohammad Soukhtanloo Neurogenic Inflammation Research Center School of MedicineMashhad University of Medical Sciences Pharmacological Research Center of Medicinal Plants School of MedicineMashhad University of Medical Sciences Department of Physiology School of MedicineMashhad University of Medical Sciences Neurocognitive Research Center and Department of Pharmacology School of MedicineMashhad University of Medical Sciences Department of Biochemistry School of MedicineMashhad University of Medical Sciences

Objective： To evaluate the effect of Nigella sativa （NS） extract on memory performance and its possible mechanisms in scopolamine （Sco）-induced spatial memory impairment model using Morris water maze test. Methods： Thirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco （2 mg/kg, intraperitoneally） 30 min before each trail in Morris water maze test. Sco＋NS 200 and SCO＋NS 400 groups were daily treated by 200 or 400 mg/kg of NS （intraperitoneally） for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase （ACHE） activity and oxidative stress criteria in cortical tissues. Results： Time latency and path length in the Sco group were significantly higher than in the control group （P〈0.01）, while the SCO＋NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group （P〈0.01）. AChE activity in the cortical tissues of the Sco group was significantly higher than the control group （P〈0.01）, while AChE activity in the Sco＋NS 200 and Sco＋NS 400 groups was lower than the Sco group （P〈0.01）. Following Sco administration, malondialdehyde （MDA） concentrations were increased （P〈0.01） in comparison with the control group, while cortical total thiol content decreased （P〈0.01）. Pretreatment with extracts caused a significant elevation in cortical total thiol content （P〈0.01） and reduction in cortical MDA concentration （P〈0.01） compared with the Sco group. Conclusions： Hydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.

关键词： Nigella sativa spatial memory morris water maze oxidative stress

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Effects of electromagnetic radiation on spatial memory and synapses in rat hippocampal CA1

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Neural Regeneration Research 2012年第16期7卷 1248-1255页

作者： Yuhong Li Changhua Shi Guobing Lu Qian Xu Shaochen Liu Chengde Medical University Chengde 067000 Hebei Province China

In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation （0.52 1.08 W/kg） was delivered to 8-week-old Wistar rats 2 hours per day for 1 month, behavioral changes were examined using the Morris water maze. Compared with the sham-irradiated rats, the irradiated rats exhibited impaired performance. Morphological changes were investigated by examining synaptic ultrastructural changes in the hippocampus. Using the physical dissector technique, the number of pyramidal neurons, the synaptic profiles, and the length of postsynaptic densities in the CA1 region were quantified stereologically. The morphological changes included mitochondrial degenerations, fewer synapses, and shorter postsynaptic densities in the radiated rats. These findings indicate that mobile phone radiation can significantly impair spatial learning and reference memory and induce morphological changes in the hippocampal CA1 region.

关键词： mobile phone memory Morris water maze electron microscopy synapse postsynaptic density quantitative analysis ultrastructure neural regeneration

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memory materials and devices:From concept to application

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InfoMat 2020年第2期2卷 261-290页

作者： Zhenhan Zhang Zongwei Wang Tuo Shi Chong Bi Feng Rao Yimao Cai Qi Liu Huaqiang Wu Peng Zhou State Key Laboratory of ASIC and System School of MicroelectronicsFudan UniversityShanghaiChina Key Laboratory of Microelectronic Devices and Circuits(MOE) Institute of MicroelectronicsPeking UniversityBeijingChina Key Laboratory of Microelectronic Devices and Integrated Technology Institute of MicroelectronicsChinese Academy of SciencesBeijingChina College of Materials Science and Engineering Shenzhen UniversityShenzhenChina Institute of Microelectronics Tsinghua UniversityBeijingChina

memory cells have always been an important element of information technology.With emerging technologies like big data and cloud computing,the scale and complexity of data storage has reached an unprecedented peak with a much higher requirement for memory technology.As is well known,better data storage is mostly achieved by miniaturization.However,as the size of the memory device is reduced,a series of problems,such as drain gate-induced leakage,greatly hinder the performance of memory units.To meet the increasing demands of information technology,novel and high-performance memory is urgently needed.Fortunately,emerging memory technologies are expected to improve memory performance and drive the information revolution.This review will focus on the progress of several emerging memory technologies,including two-dimensional material-based memories,resistance random access memory(RRAM),magnetic random access memory(MRAM),and phasechange random access memory(PCRAM).Advantages,mechanisms,and applications of these diverse memory technologies will be discussed in this review.

关键词： memory MRAM PCRAM RRAM two-dimensional material

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