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The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.
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This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 μmol·L~(-1)) baicalin group, medium-dose(10 μmol·L~(-1)) baicalin group, high-dose(20 μmol·L~(-1)) baicalin group, and minocycline(10 μmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1β(IL-1β), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1β, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1β, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1β, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1β, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.
Subject(s)
Animals , Mice , Flavonoids , Inflammation/genetics , Interferon-gamma , Lipopolysaccharides/adverse effects , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolismABSTRACT
Epilepsy is a chronic and severe neurological disorder that has negative effects on the autonomous activities of patients. Functionally, Trem2 (triggering receptor expressed on myeloid cells-2) is an immunoglobulin receptor that affects neurological and psychiatric genetic diseases. Based on this rationale, we aimed to assess the potential role of Trem2 integration with the PI3K/Akt pathway in epilepsy. We used microarray-based gene expression profiling to identify epilepsy-related differentially-expressed genes. In a mouse hippocampal neuron model of epilepsy, neurons were treated with low-Mg extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-of-function approach with Trem2, neuronal apoptosis and its related factors were assessed by flow cytometry, RT-qPCR, and Western blot analysis. In a pilocarpine-induced epileptic mouse model, the malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) content and superoxide dismutase (SOD) and glutathione-peroxidase (GSH-Px) activity in the hippocampus were determined, and the protein expression of Trem2 was measured. In addition, the regulatory effect of Trem2 on the PI3K/Akt pathway was analyzed by inhibiting this pathway in both the cell and mouse models of epilepsy. Trem2 was found to occupy a core position and was correlated with epilepsy. Trem2 was decreased in the hippocampus of epileptic mice and epileptic hippocampal neurons. Of crucial importance, overexpression of Trem2 activated the PI3K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3K/Akt pathway through over-expression of Trem2 alleviated oxidative stress, as shown by the increased expression of SOD and GSH-Px and the decreased expression of MDA and 8-OHdG. The current study defines the potential role of Trem2 in inhibiting the development of epilepsy, indicating that Trem2 up-regulation alleviates hippocampal neuronal injury and oxidative stress, and inhibits neuronal apoptosis in epilepsy by activating the PI3K/Akt pathway.
Subject(s)
Animals , Male , Apoptosis , Cells, Cultured , Epilepsy , Metabolism , Gene Expression Profiling , Hippocampus , Metabolism , Membrane Glycoproteins , Metabolism , Mice, Inbred ICR , Neurons , Metabolism , Oxidative Stress , Phosphatidylinositol 3-Kinase , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Receptors, Immunologic , Metabolism , Signal Transduction , Up-RegulationABSTRACT
Objective To compare the characteristics of tremor and improvement after acute levodopa challenge test in young onset Parkinson's disease(YOPD)and late onset Parkinson's disease(LOPD)with a cross-sectional study. Methods From Match to September,2017,70 Parkinson's disease inpatients with rest or postural tremor in at least one extremity were included,in which 23 patients were in YOPD group,and other 47 in LOPD group according to their ages of onset.They finished acute levodopa challenge test and were analyzed for dominant tremor frequen-cy,amplitude and rhythm under resting state,posturing and holding 1000 grams state,respectively. Results YOPD group was younger(t=-2.423,P<0.01)with lower Hoehn-Yahr stage(χ2=-4.604,P<0.05),and needed less equivalent dose of levodopa at early stage(first five years)(t=-2.119,P<0.05).There was a bigger ratio of patients with rest tremor in frequency of four to six Hz in YOPD group than in LOPD group(χ2=3.896,P<0.05). Rigidity and bradykinesia scores of LOPD group positively correlated with the course of disease (r=0.34, P<0.05),while it was not found in YOPD group. Conclusion Tremor expresses most in the classical way in YOPD patients,and tremor analysis could help to diagnose young adults. Both YOPD and LOPD patients get well in acute levodopa challenge test, while YOPD patients need less equivalent dose of levodopa at early stage.
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Analisar sob a ótica da Nova História Cultural os vestígios da loucura em Barbacena no conto de João Guimarães Rosa Sorôco, sua mãe, sua fi lha. Metodologia: O percurso metodológico contempla o universo da Nova História Cultural, pautado nas representações e apropriações apresentadas neste campo, pelo historiador Roger Chartier. Destacaram-se três categorias temáticas: As representações da loucura no trem de doido; Os vestígios da loucura presentes nos atos da mãe e filha de Sorôco; Convivendo com a loucura sob o olhar de Sorôco. Resultado/Discussão: O trem é descrito por Guimarães Rosa como um local inóspito, repleto de marcas da tristeza dos familiares que a cada viagem do trem embarcam seus parentes que não voltarão mais. Ele compara os vagões repletos de grades a uma prisão. O autor se propõem a caracterizar a loucura nos trejeitos, modo de vestir e atos das duas personagens, que como coadjuvantes, compuseram a representação da loucura da época. Considerações Finais: Os sentimentos apresentados pelo autor no conto estão presentes na atualidade, a sociedade ainda se indigna com tamanha cantoria e expressão dos ditos malucos, loucos, alienados. Os trens não tem mais celas, mas suas representações, as imagens formadas no imaginário sobre o fato histórico não podem se apagar.
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History, 20th Century , History of Nursing , Mental Disorders , Railroads , History , LiteratureABSTRACT
Objective To detect the differences of triggering receptor expressed on myeloid cells-1 (TREM-1) and cyclo-oxygenase-2 (COX-2) expressions in rectal cancer tissues and carcinoma adjacent tissues so as to explore the relationship between the two factors and clinical pathological characteristics and their effects on the patients` survival.Methods The expressions of TREM-1 and COX-2 were analyzed in 68 cases of rectal cancer tissues and 58 cases of carcinoma adjacent tissues with the method of immunohistochemical staining.We made a regular follow-up of the patients, analyzed the relationship between the two factors and prognosis of rectal cancer.Results The positive expression rates of TREM-1 and COX-2 in rectal cancer tissues were higher than those in carcinoma adjacent tissues (P<0.05).The expression of TREM-1 was related to lymph node metastasis, while COX-2 was related to pathological stage and lymph node metastasis (P<0.05).However, the two factors were not related to age, sex, histological differentiation or tumor size.The expressions of the two factors were positively correlated (r=0.550, P<0.001).The overall survival (OS) of TREM-1 and COX-2 positive expression groups was shorter than that of the negative groups (P<0.05).Cox multiple regression analysis showed that the expression of TREM-1, pathological stage, lymph node metastasis and tumor size affected the prognosis.Conclusion The expressions of COX-2 and TREM-1 in rectal cancer increase, suggesting that the two factors may promote the development and lymph node metastasis of rectal cancer, and the expressions of the two factors are related to the patients` poor prognosis.
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Alzheimer disease (AD) is a common neurodegenerative disease in the elderly, but nowadays the pathogenesis of AD is unclear. Myeloid cell 2 trigger receptor (TREM2) is one of the most famous and most common rare mutations in neurodegenerative disease research, and its functional site mutation can significantly increase the incidence of AD. In this paper, we summary the structure, localization, and function and related signaling pathways of TREM2, review the latest epide?miological findings of TREM2 associated with the pathogenesis of AD, and speculate on the possible role of TREM2 in the progression of this disease, as well as the expression of TREM2 and the role of soluble TREM2 in AD brain are further elucidated. Based on the potential protective effect of TREM2 in the pathogenesis of AD, Therefore, targeting TREM2 may provide new opportunities and a reference for AD treatment. As the TREM2 variant appears to be widely involved in neurodegenerative diseases, there is an urgent need to further study the function of TREM2 in the brain and to find its ligands involved in TREM2-mediated signaling transduction and its specific role in AD pathogenesis.
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The effects of atropine (non selective muscarinic antagonist) and ZM241385 (A2A receptors antagonist) in the cisatracurium-induced drastic (100%) level of fade at 50 Hz (10 s) (100% Fade) were compared in the phrenic nerve-diaphragm muscle preparations of rats indirectly stimulated at a physiological tetanic frequency (50 Hz). The lowest dose and the instant cisatracurium caused 100% Fade were investigated. Cisatracurium induced 100% Fade 15 min after being administered. Atropine reduced the cisatracurium-induced 100% Fade, but the administration of ZM241385 separately, or combined with atropine, did not cause any effect in the cisatracurium-induced 100% Fade. Data indicate that the simultaneous blockage of M1 and M2 muscarinic receptors on motor nerve terminal by atropine is more efficient than the blockage of presynaptic A2A receptors for a safer recovery of patients from neuromuscular blockade caused by cisatracurium.
Os efeitos de atropina e ZM241385 (antagonistas de receptores A2A) no drástico (100%) nível de fadiga (100% Fadiga) produzido pelo cisatracúrio a 50 Hz (10 s) foram comparativamente investigados em preparações nervo frênico músculo diafragma isolado de ratos indiretamente estimuladas com a frequência fisiológica tetanizante de 50 Hz. A menor dose e o instante no qual cisatracúrio causou 100% Fadiga foram pesquisados. O cisatracúrio induziu 100% Fadiga 15 min depois de ser administrado. A atropina reduziu a fadiga de 100% causada pelo cisatracúrio, mas ZM241385, ou a administração combinada de atropina com ZM241385, não causou qualquer efeito na 100% Fadiga produzida pelo cisatracúrio. Os dados indicam que o bloqueio simultâneo dos receptores muscarínicos M1 e M2 no terminal nervoso motor pela atropina é mais eficiente do que o bloqueio dos receptores pré-sinápticos A2A no auxilio da recuperação mais segura do bloqueio da transmissão neuromuscular causada por cisatracúrio.
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Humans , Atropine , Adenosine , Receptors, Muscarinic , Muscle Fatigue , Neuromuscular Blocking AgentsABSTRACT
Objective To study the expression of triggering receptor expressed on myeloid cells-1 (Trem-1)in psoriatic vulgaris and normal skin tissues and blood,and to explore the potential pathogenesis of psoriasis.Methods Immunohistochemistry and Real-time PCR were used to detect the expression of Trem-1 in the blood and tissues of normal skin and psoriasis.Results The positive expression rate of Trem-1 in psoriatic lesion was significantly higher than normal tissue.Trem-1 was expressed in the whole epidermis,with a significant difference (P<0.05). The mRNA expression of Trem-1 was significantly higher in psoriatic skin tissues and blood than in normal skin tissues and blood (P<0.05).Moreover,the mRNA expression of Trem-1 was positively correlated with PASI (P<0.05).Conclusion Abnormal expression of Trem-1 might be related to the pathogenesis of psoriasis.Trem-1 will cure psoriasis vulgaris as the potential therapeutic target.
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Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions.
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Animals , Rats , Aspartate Aminotransferases , Creatine , Enzyme-Linked Immunosorbent Assay , Hematologic Tests , Inflammation , Intestinal Mucosa , Intestine, Small , Kidney , Leukocyte Count , Liver , Lung , Models, Animal , Multiple Organ Failure , Plasma , Platelet Count , Rats, Wistar , Sepsis , StomachABSTRACT
The triggering receptor expressed on myeloid cells (TREM) family, which is abundantly expressed in myeloid lineage cells, plays a pivotal role in innate and adaptive immune response. In this study, we aimed to identify a novel receptor expressed on hematopoietic stem cells (HSCs) by using in silico bioinformatics and to characterize the identified receptor. We thus found the TREM-like transcript (TLT)-6, a new member of TREM family. TLT-6 has a single immunoglobulin domain in the extracellular region and a long cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motif-like domains. TLT-6 transcript was expressed in HSCs, monocytes and macrophages. TLT-6 protein was up-regulated on the surface of bone marrow-derived and peritoneal macrophages by lipopolysaccharide stimulation. TLT-6 exerted anti-proliferative effects in macrophages. Our results demonstrate that TLT-6 may regulate the activation and proliferation of macrophages.
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Humans , Adaptive Immunity , Computational Biology , Computer Simulation , Cytoplasm , Hematopoietic Stem Cells , Immunoglobulins , Macrophages , Macrophages, Peritoneal , Monocytes , Myeloid CellsABSTRACT
Nasu-Hakola disease (NHD) is a rare autosomal recessive neuropsychiatric disorder characterized by bone cysts, fractures, and cognitive impairment. Two genes are responsible for the development of NHD; TYROBP and TREM2. Although it presents with typical signs and symptoms, diagnosing this disease remains difficult. This case report describes a male with NHD with no family or past history of bone fractures who was diagnosed using exome sequencing. His frontal lobe psychiatric symptoms recovered partially following treatment with sodium valproate, but not with an antipsychotic.
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Humans , Male , Bone Cysts , Consanguinity , Exome , Fractures, Bone , Frontal Lobe , Sodium , Valproic AcidABSTRACT
OBJECTIVE: To investigate the role of TREM-1 in tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion from lipopolysaccharide-induced mice macrophage cell lines RAW264.7. METHODS: Designing and synthesizing small interfering RNA (siRNA) with high intangerference ratio, then constructing pLKO1.1-puro-TREM-1 The mice macrophage cell lines RAW264.7 were divided into four groups: control group (control); lipopolysaccharide group (LPS); empty plasmid group (pLKO1.1) - just transfected with pLKO1.1; interference group (siRNA) - transfected with pLKO1.1-puro-TREM1.24 h after stimulation with LPS, real-time PCR was used to detect the mRNA levels of TREM-1, TNF-α and IL-1β respectively. The concentrations of TNF-α and IL-1β were assayed by ELISA. RESULTS: In siRNA group, the mRNA levels of TREM-1, TNF-α and IL-1β were decreased significantly (P<0.01): moreover, the concentrations of TNF-α and IL-1β were lower than other groups significantly (P<0.01). CONCLUSION: Small interfering RNA may reduce TNF-α, IL-1β secretion in LPS-induced macrophage 264.7 through inhibiting the expression of TREM-1 gene.
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There is a higher sepsis rate in the intensive care unit (ICU) patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s) triggering receptor expressed on myeloid cells-1 (sTREM-1) suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI) in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT) and C-reactive protein (CRP) in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR-146a, miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.
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La Enfermedad de Alzheimer es un problema neurodegenerativo cuyas causas aún no están bien definidas, sin embargo, existen distintas relaciones entre cambios genéticos y la presencia de los síntomas y signos de la enfermedad. Entre ellos están los genes ya conocidos APP, PSEN1 y PSEN2. Con los nuevos avances científicos, se conocen nuevos genes relacionados a esta enfermedad como lo son el gen CHAT, APOE, 5-HTTLPR, SORLI, NINJ2, CST3, EXOC3L2, CLU, NGFR, TREM2, APOC1, ACE, SLC2A14, entre otros. La relación entre estos genes y la enfermedad es muy estrecha y podría ser la brecha en encontrar una posible cura.
Alzheimer's disease is a neurodegenerative problem which cause is not well defined, however, there are different relationships between genetic changes and the presence of symptoms and signs of the disease. Among them, there are some well known such as the APP gene, PSEN 1 and PSEN2. With new scientific advances now we know new genes associated with the disease such as the CHAT, APOE, 5-HTTLPR, SORLI, NINJ2, CST3, EXOC3L2, CLU, NGFR, TREM2, APOCI, ACE, SLC2A14 genes, among others. The knowledge about these genes and the disease could help to find the cure.
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Triggering receptor expressed on myeloid cells-1 ( TREM-1 ) is one of immunoglobulin superfamilies found recently.TREM-1 is a crucial molecule for the triggering and amplification of inflammatory response and promote the reduction of in anti-inflammatory factor by crosslinking reaction with its ligand after being activated,or increasing the level of transcription factor.This study shows that TREM-1 may be claimed as a marker of infection,and the blockade of TREM-1 may be a new approach to inflammatory diseases.This study summarizes its structure,signal transduction,expression,accommodation and clinical application.
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Objective To investigate the expression and significance of human TREM-1 mRNA in patients with (biliary) infection. Methods Peripheral blood of 32 patients with biliary infection and 7 healthy volunteers were (collected). TREM-1 mRNA was determined by semi-quantitative RT-PCR. TNF-? was determined by ELISA method. Results The values of TREM-1/?-actin of control group was 0.48?0.072, while those of biliary infection group in 1d, 2d, 3d, 7d were 0.93?0.070,0.90?0.060,0.82?0.092,0.66?0.062 respectively (P