scholarly journals NAD+ Improved Experimental Autoimmune Encephalomyelitis by Regulating SIRT1 to Inhibit PI3K/ Akt /mTOR Signaling Pathway

2021 ◽  
Author(s):  
Jinli Wang ◽  
Xueqin Song ◽  
Guojun Tan ◽  
Pengtao Sun ◽  
Li Guo ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Neurological Function ◽  
Control Group ◽  
Data Sets ◽  
Function Score ◽  
Autoimmune Encephalomyelitis ◽  
Cell Experiment ◽  
Sirt1 Inhibitor ◽  
And Control ◽  
Experimental Autoimmune

Abstract Objective: To investigate the effect of NAD+ on thymus autophagy in experimental autoimmune encephalomyelitis (EAE) mice through SIRT1. Methods: Data sets GSE135511 and GSE131279 related to fatty liver in multiple sclerosis were downloaded from GEO database to search for differentially expressed genes. KEGG and GO pathway enrichment analysis was performed to construct PPI network, identify important modules and hub genes, and analyze the expression of hub genes. Animal experiments: Forty female C57BL/6 mice were randomly divided into 4 groups: control group, EAE group, NAD+ group and SIRT1 inhibitor group. The EAE model was prepared by MOG35-55 polypeptide immunoassay. The NAD+ group and SIRT1 inhibitor group were treated with NAD+ drug and fed for 4 weeks. The neurological function scores of the mice in each group were evaluated weekly. Cell experiment: The thymus tissues of wild-type mice were removed, ground and filtered into single-cell suspension, and then cultured. The thymus tissues were divided into four groups: control group, EAE group, NAD+ group and SIRT1 inhibitor group. MOG 35-55 (1μg/ mL) was given to induce EAE model in vitro. Both the NAD+ group and the SIRT1 inhibitor group were treated with NAD+. The expression of LC-3B was observed by immunofluorescence. The expressions of p-PI3K, p-AKT, p-mTOR, P62, Beclin1, LC-3B and SIRT1 were detected by WB. Results: Data sets GSE135511 and GSE131279 contained 95 up-regulated DEGs and 89 down-regulated DEGs. Enrichment analysis showed that it was mainly concentrated in PI3K-Akt-mTOR and autophagy pathway. SIRT1 was low expressed in the disease group. The EAE group, the NAD+ group and the SIRT1 inhibitor group all showed different degrees of morbidity. At week 2, there was no significant difference between the EAE group and the NAD+ group and the SIRT1 inhibitor group, but the neurological function score of the SIRT1 inhibitor group was significantly higher than that of the NAD+ group. The neurological function score of SIRT1 inhibitor group was the highest at 3 and 4 weeks. WB test showed that the expressions of P62, Beclin1, LC-3B and SIRT1 were the highest in the NAD+ group, while the expressions of p-PI3K, p-Akt and p-mTOR were the highest in the EAE group, followed by the SIRT1 inhibitor group, the NAD+ group and the control group. Cell experiment: Immunofluorescence showed that the fluorescence intensity of LC-3B in NAD+ group was the highest, followed by SIRT1 inhibitor group, EAE group, and control group. WB test showed that the expressions of P62, Beclin1, LC-3B and SIRT1 were the highest in the NAD+ group, followed by SIRT1 inhibitor group, EAE group and control group. The expressions of p-PI3K, p-AKT and p-mTOR were the highest in EAE group, followed by SIRT1 inhibitor group, NAD+ group and control group. Conclusion: NAD+ exerted a protective effect on EAE mice by inhibiting PI3K/ Akt /mTOR signaling pathway through SIRT1, and prevented EAE mice from sustained damage.

scholarly journals Effect of Voluntary Training after the Induction of Experimental Autoimmune Encephalomyelitis on Some Myelin-Producing Proteins in Female C57BL/6 Mice

2021 ◽  
Author(s):  
Yasaman Honarmandnasab ◽  
Mohammad Reza Kordi ◽  
Abbas Ali Gaeini
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Wheel Running ◽  
Clinical Score ◽  
Exercise Group ◽  
Voluntary Exercise ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Healthy Control ◽  
And Control ◽  
Experimental Autoimmune

Introduction: The aim of the present study was to investigate the effect of voluntary training period after the induction of experimental autoimmune encephalomyelitis (EAE) on some myelin-producing proteins in C57BL/6 female mice. Methods: In this experimental study first 28 mice, which were 6-8 weeks old, were purchased and were randomly divided into three groups. Exercise activity (n=12), healthy control (n=8) and experimental autoimmune encephalomyelitis (EAE) control (n=8). Voluntary exercise group did exercises, 1 hour, 5 days a week for 4 weeks after induction of EAE and having the clinical score one for two days in a row. 48 hours after final exercise section, the mice were killed and immunohistochemistry was used to evaluate the expression of MBP and CNPase proteins. Using SPSS version 16 software, multiple analysis of variance and LSD post hoc test were used to examine the groups' data differences. Results: The results showed that the expression of both proteins as a result of voluntary exercise had a significant increase in the exercise group compared to the EAE control group ( p<0.05).( in White Matter: MBP, Wheel Running and Control EAE, P= .017; Wheel Running and Healthy Control, P= .001; CNPase, Wheel Running and Control EAE, P= .015; Wheel Running and Healthy Control, P= .000; in Gray Matter: MBP, Wheel Running and Control EAE, P= .000; Wheel Running and Healthy Control, P= .000; CNPase, Wheel Running and Control EAE, P= .005; Wheel Running and Healthy Control, P= .001. Conclusion: Voluntary exercise may have a positive effect on increasing myelination in treatment and control of MS.

scholarly journals Analysis of Risk Factors in Dementia Through Machine Learning

2020 ◽  
pp. 1-17
Author(s):  
Francisco Javier Balea-Fernandez ◽  
Beatriz Martinez-Vega ◽  
Samuel Ortega ◽  
Himar Fabelo ◽  
Raquel Leon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Optimization Algorithms ◽  
Progressive Increase ◽  
Control Group ◽  
Data Sets ◽  
Modifiable Factors ◽  
Validation Set ◽  
The One ◽  
And Control ◽  
Potential Tool

Background: Sociodemographic data indicate the progressive increase in life expectancy and the prevalence of Alzheimer’s disease (AD). AD is raised as one of the greatest public health problems. Its etiology is twofold: on the one hand, non-modifiable factors and on the other, modifiable. Objective: This study aims to develop a processing framework based on machine learning (ML) and optimization algorithms to study sociodemographic, clinical, and analytical variables, selecting the best combination among them for an accurate discrimination between controls and subjects with major neurocognitive disorder (MNCD). Methods: This research is based on an observational-analytical design. Two research groups were established: MNCD group (n = 46) and control group (n = 38). ML and optimization algorithms were employed to automatically diagnose MNCD. Results: Twelve out of 37 variables were identified in the validation set as the most relevant for MNCD diagnosis. Sensitivity of 100%and specificity of 71%were achieved using a Random Forest classifier. Conclusion: ML is a potential tool for automatic prediction of MNCD which can be applied to relatively small preclinical and clinical data sets. These results can be interpreted to support the influence of the environment on the development of AD.

scholarly journals The induced dose of experimental autoimmune encephalomyelitis was not determinant and proportional to histopathological findings

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Maiara Carolina Perussolo ◽  
Bassam Felipe Mogharbel ◽  
Lucia de Noronha ◽  
Katherine Athayde Teixeira de Carvalho
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Histopathological Findings ◽  
The Brain ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. It presents a diversity of neurologic signs and symptoms as well the incapacities. Since the need for advances in MS treatment, many studies are for new therapeutic technologies, mainly through using preclinical models as experimental autoimmune encephalomyelitis (EAE). This study aimed to observe and analyze the development in Lewis rats-induced model of EAE. Methods It was used 23 females of Rattus norvegicus, from 6 to 8 weeks, weighing around 170 g. Of 23 rats, 19 underwent EAE induction distributed in six groups to establish the evolution of clinical signs. B. pertussis toxin (PTX) doses were 200, 250, 300, 350–400 ng, and four animals as the control group. The animals had weight and scores analyzed daily, starting seven and ending 24 days after induction. Then, all animals were euthanized, and the brain and spinal cord were collected for histopathological analyses. Results The results showed that the dose of 250 ng of PTX induced de higher score and weight reduction. All groups who received the PTX demonstrated histopathological findings. Those characterized as leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brain. In the spinal cord, the loosening of the myelinated fibers was observed by increasing the axonal space in all tested doses of PTX. Conclusions EAE was not dose-dependent. Histopathological findings do not proportionally related to clinical signs, as in human patients with MS.

Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 557-560 ◽  
Author(s):  
M Kawajiri ◽  
M Mogi ◽  
M Osoegawa ◽  
T Matsuoka ◽  
K Tsukuda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Neurological Diseases ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Disability Status ◽  
Scale Scores ◽  
Inflammatory Neuropathies ◽  
And Control

We previously demonstrated that angiotensin II acts as a crucial neuroprotective factor after neural injury through angiotensin II type-2 (AT2) receptor signaling. Although the pathway is known to play an important role in the development of experimental autoimmune encephalomyelitis, cerebrospinal fluid (CSF) angiotensin II levels in patients with multiple sclerosis (MS) have never been studied. To clarify the significance of angiotensin II in MS, we assayed angiotensin II concentrations using an established enzyme-linked immunoabsorbent assay in CSF samples from patients with MS ( n = 21), patients with inflammatory neuropathies (IN) ( n = 23) and control individuals who did not have either of the neurological diseases or any other disease that might affect the angiotensin II levels in the CSF (control) ( n = 24). Angiotensin II levels in the CSF were 3.79 ± 1.54 pg/ml in the MS group, 5.13 ± 2.27 pg/ml in the IN group and 6.71 ± 2.65 pg/ml in the control group. The angiotensin II levels in the CSF of the MS group were significantly lower than in the control group ( p = 0.00057). Angiotensin II concentration in the CSF tended to have a negative correlation with the Kurtzke’s Expanded Disability Status Scale scores during MS relapse ( p = 0.0847). These findings suggest that reduced levels of intrathecal angiotensin II may be related to the abnormal neural damage and repair processes in MS.

scholarly journals Oral Administration of Probiotic Enterococcus Durans Ameliorates Experimental Autoimmune Encephalomyelitis in Mice

2021 ◽  
Author(s):  
Seyed Abdollah Samani ◽  
◽  
Mohamad Raman Moloudi ◽  
Rashid Ramezan Zadeh ◽  
Mohammad Abdi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Control Group ◽  
Immunomodulatory Activity ◽  
Spinal Cord Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Enterococcus Durans ◽  
Experimental Autoimmune

Introduction: Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. In this study, the potential of Enterococcus durans and three various strains of lactobacilli (lacto-mix), Including L.rhamnosus, L.casei, and L.plantarum for prevention of Experimental Autoimmune Encephalomyelitis (EAE) features were evaluated. Methods: C57BL/6 female mice were inoculated with (MOG35-55) / (CFA) to induce EAE. Different groups (five groups: n = 6 in each group) of animals received saline or probiotics by oral gavage with 200 µl of lactobacilli (1.5 *108 CFU/ml) for 2 week before the immunization and during the test for one month. Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in the probiotic-treated animals. Pro-inflammatory cytokines (IL-17 and IFN-g) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (p <0.01), while in the spinal cord tissue there was a decrease in IL-17 in those animals treated with the Lacto-mix and Edu + Lacto- mix (p <0.01) and a significant decrease in IFN-g in those animals that received Edu (p <0.05). Western blot analysis of MMP-9 and MBP proteins showed a decrease and increase in treatment and EAE groups, compared to the normal control group respectively. Conclusion: our data suggest that probiotic Enterococcus durans and lacto-mix had a preventive effect against EAE but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials.

Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis

1994 ◽  
Vol 77 (5) ◽  
pp. 2341-2347 ◽  
Author(s):  
C. Le Page ◽  
A. Ferry ◽  
M. Rieu
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Autoimmune Response ◽  
Spinal Cord Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Body Mass Loss ◽  
Different Types ◽  
And Control ◽  
Experimental Autoimmune

We examined whether physical exercise affected the development of an autoimmune response, experimental autoimmune encephalomyelitis (EAE), which is a demyelinating disease leading to paralysis. EAE was inducted on day 0, in rats of both sexes, by injecting them with spinal cord tissue in adjuvant. From days 1 to 10 after injection, exercised rats (n = 55) ran on a treadmill (60–120 min/day) before the onset of the paralytic disease. Clinical signs of the disease (ataxia, paralysis, and body mass loss) were examined in exercised and control rats (n = 54). Three types of EAE were induced: monophasic, acute, and chronic relapsing (CR)-EAE (3 bouts of disease, CR-EAE 1, 2, and 3, separated by remissions). Exercise significantly delayed the onset of CR-EAE 1 (P = 0.001) and the 1st day of maximum severity of CR-EAE 1 (P = 0.001) and CR-EAE 2 (P = 0.002). Moreover, the duration of CR-EAE 1 was significantly decreased in exercised rats compared with control rats (P = 0.004). The peak severity of the different types of EAE was not modified by exercise. The present study indicates that endurance exercise during the phase of induction of EAE diminished lightly only one type of EAE (CR-EAE) and therefore did not exacerbate the autoimmune disease.

An Exploration of the Effects of Tibetan Yoga on Patients’ Psychological Well-Being and Experience of Lymphoma: An Experimental Embedded Mixed Methods Study

2016 ◽  
Vol 12 (1) ◽  
pp. 31-54 ◽  
Author(s):  
Isabel Leal ◽  
Joan Engebretson ◽  
Lorenzo Cohen ◽  
Maria Eugenia Fernandez-Esquer ◽  
Gabriel Lopez ◽  
...  
Keyword(s):  
Well Being ◽  
Control Group ◽  
Data Sets ◽  
Transformation Techniques ◽  
Treatment Groups ◽  
Model Combining ◽  
Embedded Design ◽  
Cancer Experience ◽  
And Control

As an emergent care model combining conventional with complementary therapies, integrative interventions challenge evaluation, necessitating approaches capable of capturing complex, multilevel interactions. This article evaluates the effects of a Tibetan yoga intervention on lymphoma patients’ quality of life and cancer experience. Our methodological aims were to explore differences in therapeutic effect between treatment and control group using qualitative data, and explain equivocal findings between data sets. Use of both data transformation techniques—qualitizing and quantitizing—within an experimental embedded design comparing and integrating data between data sets and treatment groups allowed us to develop this innovative evaluative approach. Findings clarify convergence and divergence between data sets, explore participants’ complex cancer experience, and capture dimensions and intervention effects inaccessible through either method alone.

Pharmacotherapy with 17β-estradiol and progesterone prevents development of mouse experimental autoimmune encephalomyelitis

2010 ◽  
Vol 1 (1) ◽  
Author(s):  
Laura Garay ◽  
Maria Claudia Gonzalez Deniselle ◽  
Lobke Gierman ◽  
Analia Lima ◽  
Paulina Roig ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Signs ◽  
Proteolipid Protein ◽  
Inflammatory Cells ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
Mouse Experimental Autoimmune Encephalomyelitis ◽  
And Control ◽  
Experimental Autoimmune

Abstract: Pregnant women with multiple sclerosis (MS) show disease remission in the third trimester concomitant with high circulating levels of sex steroids. Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for MS. Previous studies have shown that monotherapy with estrogens or progesterone exert beneficial effects on EAE. The aim of the present study was to determine if estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial protection from EAE.: A group of mice received single pellets of progesterone (100 mg) and 17 β-estradiol (2.5 mg) subcutaneously 1 week before EAE induction, whereas another group were untreated before EAE induction. On day 16 we compared the two EAE groups and control mice in terms of clinical scores, spinal cord demyelination, expression of myelin basic protein and proteolipid protein, macrophage cell infiltration, neuronal expression of brain-derived neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic protein (GFAP)-immunopositive astrocytes.: Clinical signs of EAE were substantially attenuated by estrogen and progesterone treatment. Steroid cotherapy prevented spinal cord demyelination, infiltration of inflammatory cells and GFAP: Cotherapy with estrogen and progesterone inhibits the development of major neurochemical abnormalities and clinical signs of EAE. We suggest that a combination of neuroprotective, promyelinating and immuno-suppressive mechanisms are involved in these beneficial effects.

scholarly journals Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes

2021 ◽  
Author(s):  
Yue Lang ◽  
Fengna Chu ◽  
Lingling Liu ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Nlrp3 Inflammasome ◽  
Demyelinating Disease ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Treatment Groups ◽  
Prevention And Treatment ◽  
Nlrp3 Inflammasomes ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5mg/kg/i.p and 20 mg/kg/i.p) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κBp65, and phosphorylated-p65 were determined by Western blotting. Serum levels of inflammatory cytokines were measured by Cytometric Bead Array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.

BMSCs transplantation downregulated NF-κB signaling pathways by being induced to differentiate into neurons in Experimental autoimmune encephalomyelitis (EAE) animal model

2020 ◽  
Author(s):  
Guo-yi Liu ◽  
Fan-yi Kong ◽  
Shu Ma ◽  
Li-yan Fu ◽  
Jia Geng
Keyword(s):  
Animal Model ◽  
Survival Rate ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neurological Function ◽  
Autoimmune Encephalomyelitis ◽  
Neuroinflammatory Disease ◽  
Marrow Mesenchymal Stem Cells ◽  
Effective Therapeutic Strategy ◽  
Immunofluorescence Labeling ◽  
Experimental Autoimmune

Abstract Background: Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity and poorly find an effective therapeutic strategy. Currently, experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS.Methods: In our study, we performed flow cytometry to identify BMSCs. To systematically evaluate whether BMSCs can be differentiate into neuron cells, astrocytes and oligodendrocyte, we analyzed the biomarkers by immunofluorescence labeling. We demonstrated the effect of bone marrow mesenchymal stem Cells (BMSCs) transplant on the EAE animal model, and determined the expression of MAP-2, GFAP, and MBP in the cortex and hippocampus of mice.Results: Our results showed that BMSCs could be induced to differentiate into neuron cells astrocytes and oligodendrocyte. BMSCs transplant improved the survival rate, neurological function scores, and obvious remyelination of mice in BMSCs transplantation group was significantly higher than EAE group (P<0.01). Morever, BMSCs transplant decreased the levels of IL-2, IL-10, IL-17 and IL-22 in the serum of EAE mice. Western blotting showed that the expression of NF-κB, IκB-α and IL-17 was decreased in BMSCs transplant group.Conclusions: Herein, our results revealed that BMSCs were transplanted into the brain of EAE mice, differentiated into neurons, improved the survival rate, neurological function recovery and the extent of demyelination in EAE mice by downregulation of NF-κB signaling pathway.

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