Displaying publications 261 - 280 of 280 in total

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  1. Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions
    Hescham S, Jahanshahi A, Meriaux C, Lim LW, Blokland A, Temel Y
    Behav Brain Res, 2015 Oct 1;292:353-60.
    PMID: 26119240 DOI: 10.1016/j.bbr.2015.06.032
    Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.
    Matched MeSH terms: Memory/physiology*
  2. Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble Aβ levels in high fat-cholesterol diet-induced rats
    Ismail N, Ismail M, Azmi NH, Bakar MFA, Yida Z, Stanslas J, et al.
    Chem Biol Interact, 2017 Sep 25;275:61-73.
    PMID: 28734741 DOI: 10.1016/j.cbi.2017.07.014
    The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.
    Matched MeSH terms: Memory Disorders/drug therapy
  3. Fulltext A Review on the Relationship between Tocotrienol and Alzheimer Disease
    Chin KY, Tay SS
    Nutrients, 2018 Jul 09;10(7).
    PMID: 29987193 DOI: 10.3390/nu10070881
    Alzheimer’s disease (AD) is plaguing the aging population worldwide due to its tremendous health care and socioeconomic burden. Current treatment of AD only offers symptomatic relief to patients. Development of agents targeting specific pathologies of AD is very slow. Tocotrienol, a member of the vitamin E family, can tackle many aspects of AD, such as oxidative stress, mitochondrial dysfunction and abnormal cholesterol synthesis. This review summarizes the current evidence on the role of tocotrienol as a neuroprotective agent. Preclinical studies showed that tocotrienol could reduce oxidative stress by acting as a free-radical scavenger and promoter of mitochondrial function and cellular repair. It also prevented glutamate-induced neurotoxicity in the cells. Human epidemiological studies showed a significant inverse relationship between tocotrienol levels and the occurrence of AD. However, there is no clinical trial to support the claim that tocotrienol can delay or prevent the onset of AD. As a conclusion, tocotrienol has the potential to be developed as an AD-preventing agent but further studies are required to validate its efficacy in humans.
    Matched MeSH terms: Memory/drug effects
  4. Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats
    Tiang N, Ahad MA, Murugaiyah V, Hassan Z
    J Pharm Pharmacol, 2020 Nov;72(11):1629-1644.
    PMID: 32743849 DOI: 10.1111/jphp.13345
    OBJECTIVES: Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect.

    METHODS: In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats.

    KEY FINDINGS: HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity.

    CONCLUSIONS: However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

    Matched MeSH terms: Memory/drug effects*
  5. Fulltext Transient prenatal ruxolitinib treatment suppresses astrogenesis during development and improves learning and memory in adult mice
    Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.
    Sci Rep, 2021 Feb 15;11(1):3847.
    PMID: 33589712 DOI: 10.1038/s41598-021-83222-z
    Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
    Matched MeSH terms: Memory/drug effects*
  6. Fulltext Executive function and attention span in euthymic patients with bipolar 1 disorder
    Normala I, Abdul HA, Azlin B, Nik Ruzyanei NJ, Hazli Z, Shah SA
    Med J Malaysia, 2010 Sep;65(3):199-203.
    PMID: 21939168
    This is a cross sectional comparison study to assess executive function and attention span in euthymic patients with bipolar 1 disorder. It compares the performance of these two cognitive domains in 40 patients with bipolar 1 disorder to that of 40 healthy normal subjects using Trail Making (TMT), Digit Span (Forward and Backward) and Verbal Fluency (VF) tests. The association between demographic, clinical characteristics and performance in all tests were examined. Patients with bipolar illness showed significant impairment with moderate to large effect sizes (VF = 0.67, TMT A = 0.52, TMT B = 0.81, Digit Forward = 0.97, Digit backward = 1.10) in all tasks of executive and attention functioning. These impairments are observed in the absence of active mood symptoms while duration and severity of illness are not found to have an effect on both cognitive domains. Medications received by patients with bipolar disorder have significant association with performance on executive tasks. The results of this study add on to the existing global evidence of cognitive impairment in bipolar illness despite its cross cultural differences. Its presence in the absence of mania, depression or mixed episode indicates that cognitive impairment is stable even after symptoms recovery.
    Matched MeSH terms: Memory
  7. Fulltext Relationships between dietary nutrients intake and lipid levels with functional MRI dorsolateral prefrontal cortex activation
    Lau H, Shahar S, Mohamad M, Rajab NF, Yahya HM, Din NC, et al.
    Clin Interv Aging, 2019;14:43-51.
    PMID: 30613138 DOI: 10.2147/CIA.S183425
    Background: Dorsolateral prefrontal cortex (DLPFC) is a key node in the cognitive control network that supports working memory. DLPFC dysfunction is related to cognitive impairment. It has been suggested that dietary components and high-density lipoprotein cholesterol (HDL-C) play a vital role in brain health and cognitive function.

    Purpose: This study aimed to investigate the relationships between dietary nutrient intake and lipid levels with functional MRI (fMRI) brain activation in DLPFC among older adults with mild cognitive impairment.

    Participants and methods: A total of 15 community-dwelling older adults with mild cognitive impairment, aged ≥60 years, participated in this cross-sectional study at selected senior citizen clubs in Klang Valley, Malaysia. The 7-day recall Diet History Questionnaire was used to assess participants' dietary nutrient intake. Fasting blood samples were also collected for lipid profile assessment. All participants performed N-back (0- and 1-back) working memory tasks during fMRI scanning. DLPFC (Brodmann's areas 9 and 46, and inferior, middle, and superior frontal gyrus) was identified as a region of interest for analysis.

    Results: Positive associations were observed between dietary intake of energy, protein, cholesterol, vitamins B6 and B12, potassium, iron, phosphorus, magnesium, and HDL-C with DLPFC activation (P<0.05). Multivariate analysis showed that vitamin B6 intake, β=0.505, t (14)=3.29, P=0.023, and Digit Symbol score, β=0.413, t (14)=2.89, P=0.045; R2=0.748, were positively related to DLPFC activation.

    Conclusion: Increased vitamin B6 intake and cognitive processing speed were related to greater activation in the DLPFC region, which was responsible for working memory, executive function, attention, planning, and decision making. Further studies are needed to elucidate the mechanisms underlying the association.

    Matched MeSH terms: Memory, Short-Term
  8. Enhancement of immune response against Mycobacterium tuberculosis HspX antigen by incorporation of combined molecular adjuvant (CASAC)
    Lew MH, Norazmi MN, Tye GJ
    Mol Immunol, 2020 Jan;117:54-64.
    PMID: 31739193 DOI: 10.1016/j.molimm.2019.10.023
    Tuberculosis (TB) is one of the deadliest human diseases worldwide caused by mycobacterial infection in the lung. Bacillus Calmette-Guerin (BCG) vaccine protects against disseminated TB in children, but its effectiveness is still questionable due to highly variable protections in adolescence and elderly individuals. Targeting the latency M.tb antigen is a recent therapeutic approach to eradicate dormant pathogen that could possibly lead to disease activation. In this study, we aimed to potentiate immune responses elicited against 16 kDa α-crystalline (HspX) tuberculosis latency antigen by incorporation of Combined Adjuvant for Synergistic Activation of Cellular immunity (CASAC). Histidine-tagged recombinant HspX protein was initially produced in Escherichia coli and purified using Ni-NTA chromatography. To evaluate its adjuvanticity, C57BL/6 mice (n = 5) were initially primed and intradermally immunised in 2-weeks interval for 4 rounds with recombinant HspX, formulated with and without CASAC. Humoral and cell-mediated immune responses elicited against HspX antigen were evaluated using ELISA and Flow Cytometry. Our findings showed that CASAC improved humoral immunity with increased antigen-specific IgG1 and IgG2a antibody response. Stronger CD8+ and Th1-driven immunity was induced by CASAC formulation as supported by elevated level of IFN-γ, TNF-α, IL-12 and IL-17A; and with low IL-10 secretion. Interestingly, adjuvanted HspX vaccine triggered a higher percentage of effector memory T-cell population than those immunised with unadjuvanted vaccine. In conclusion, CASAC adjuvant has great potential to enhance immunogenicity elicited against HspX antigen, which could be an alternative regimen to improve the efficacy of future therapeutic vaccine against Mycobacterium tuberculosis.
    Matched MeSH terms: Immunologic Memory
  9. Fulltext Micronutrient interventions on cognitive performance of children aged 5-15 years in developing countries
    Khor GL, Misra S
    Asia Pac J Clin Nutr, 2012;21(4):476-86.
    PMID: 23017305
    It is estimated that more than 200 million young children worldwide fail to reach their potential in cognitive development owing to undernutrition. Numerous studies have assessed the effects of micronutrient supplementation on growth and cognitive development in infants, toddlers and preschoolers. However, micronutrient interventions on the cognitive performance of older children are limited. This article seeks to provide an update on micronutrient interventions and cognitive outcomes among children aged 5-15 years in developing countries. A total of 13 randomized controlled trials published since 2000 were identified. Majority of these studies assessed the effects of micronutrient-fortified foods on various domains of cognitive function. Among key micronutrients assessed were iron, zinc, iodine and vitamin A. This review found a lack of consistency in the impact of micronutrient supplementation on intelligence, long term mental functions and school examination grades of the children. A beneficial effect of micronutrient supplementation on short term memory was more consistently reported. Overall, the evidence from this review for the impact of micronutrients on cognitive performance in older children remains equivocal. In light of the growing interest on the influence of nutrition on cognition, it is important that culturally-appropriate and sufficiently sensitive assessment tools be used for measuring the desired cognitive outcomes that are most likely to be affected by the nutrients under study.
    Matched MeSH terms: Memory, Short-Term
  10. Fulltext Cognitive health of older persons in longitudinal ageing cohort studies
    Ng TP
    Sains Malaysiana, 2016;45:1351-1355.
    Dementia poses a major global burden of care to society and health systems in ageing populations. The majority (over 60%) of persons with dementia in the world are found in Asia and developing countries with rapid rates of population ageing. Improving and maintaining the cognitive health of older persons is vital to national strategies for dementia prevention. Increasing numbers of population-based ageing cohort studies in the past decade have provided a better understanding of the factors that contribute to cognitive function and decline in old age. The roles of major demographic, psychosocial, lifestyle, behavioral and cardiovascular risk factors contributing to cognitive health were discussed using examples from the Singapore Longitudinal Ageing Studies. They include socio-demographic factors, particularly education and marital status, leisure time activity such as physical activity, social engagement and mental activities, psychological factors such as depression, cardiovascular and metabolic risk factors: obesity, diabetes, hypertension and dyslipidemia, and the metabolic syndrome, under-nutrition, low albumin, low hemoglobin, nutritional factors such as blood folate, B12 and homocysteine, omega-3 poly-unsaturated fatty acids, tea drinking and curcumin-rich turmeric in curry meals. These factors are found to be associated variously with cognitive functions (memory and learning, language, visuospatial, attention and information processing speed), rates of cognitive impairment and cognitive decline, or increased risk of developing MCI and progression to dementia.
    Matched MeSH terms: Memory
  11. Discrimination of stroke-related mild cognitive impairment and vascular dementia using EEG signal analysis
    Al-Qazzaz NK, Ali SHBM, Ahmad SA, Islam MS, Escudero J
    Med Biol Eng Comput, 2018 Jan;56(1):137-157.
    PMID: 29119540 DOI: 10.1007/s11517-017-1734-7
    Stroke survivors are more prone to developing cognitive impairment and dementia. Dementia detection is a challenge for supporting personalized healthcare. This study analyzes the electroencephalogram (EEG) background activity of 5 vascular dementia (VaD) patients, 15 stroke-related patients with mild cognitive impairment (MCI), and 15 control healthy subjects during a working memory (WM) task. The objective of this study is twofold. First, it aims to enhance the discrimination of VaD, stroke-related MCI patients, and control subjects using fuzzy neighborhood preserving analysis with QR-decomposition (FNPAQR); second, it aims to extract and investigate the spectral features that characterize the post-stroke dementia patients compared to the control subjects. Nineteen channels were recorded and analyzed using the independent component analysis and wavelet analysis (ICA-WT) denoising technique. Using ANOVA, linear spectral power including relative powers (RP) and power ratio were calculated to test whether the EEG dominant frequencies were slowed down in VaD and stroke-related MCI patients. Non-linear features including permutation entropy (PerEn) and fractal dimension (FD) were used to test the degree of irregularity and complexity, which was significantly lower in patients with VaD and stroke-related MCI than that in control subjects (ANOVA; p ˂ 0.05). This study is the first to use fuzzy neighborhood preserving analysis with QR-decomposition (FNPAQR) dimensionality reduction technique with EEG background activity of dementia patients. The impairment of post-stroke patients was detected using support vector machine (SVM) and k-nearest neighbors (kNN) classifiers. A comparative study has been performed to check the effectiveness of using FNPAQR dimensionality reduction technique with the SVM and kNN classifiers. FNPAQR with SVM and kNN obtained 91.48 and 89.63% accuracy, respectively, whereas without using the FNPAQR exhibited 70 and 67.78% accuracy for SVM and kNN, respectively, in classifying VaD, stroke-related MCI, and control patients, respectively. Therefore, EEG could be a reliable index for inspecting concise markers that are sensitive to VaD and stroke-related MCI patients compared to control healthy subjects.
    Matched MeSH terms: Memory, Short-Term
  12. Development of the clinical assessment scale in autoimmune encephalitis
    Lim JA, Lee ST, Moon J, Jun JS, Kim TJ, Shin YW, et al.
    Ann Neurol, 2019 03;85(3):352-358.
    PMID: 30675918 DOI: 10.1002/ana.25421
    OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale.

    METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).

    RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p

    Matched MeSH terms: Memory Disorders/etiology; Memory Disorders/physiopathology
  13. Fulltext A pilot placebo-controlled, double-blind, and randomized study on the cognition-enhancing benefits of a proprietary chicken meat ingredient in healthy subjects
    Azhar ZM, Zubaidah JO, Norjan KO, Zhuang CY, Tsang F
    Nutr J, 2013;12:121.
    PMID: 23945213 DOI: 10.1186/1475-2891-12-121
    It has long been postulated that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that could be responsible for the action of diet on brain health and cognitive function. Here, through a double-blind, randomized, placebo-controlled trial, we asked if the newly discovered chicken meat ingredient-168 (CMI-168) could be beneficial to the cognitive function in healthy adults.
    Matched MeSH terms: Memory, Short-Term
  14. MRI Markers of Mixed Pathology and Cognitive Impairment in Multiethnic Asians
    Tan CH, Hilal S, Xu X, Vrooman H, Cheng CY, Wong TY, et al.
    J Alzheimers Dis, 2020;73(4):1501-1509.
    PMID: 31958085 DOI: 10.3233/JAD-190866
    There is a need to elucidate the combined influence of neurodegeneration and cerebrovascular disease (CeVD) on cognitive impairment, especially in diverse populations. Here, we evaluated 840 multiethnic individuals (mean age = 70.18) across the disease spectrum from the Epidemiology of Dementia in Singapore study. First, we determined whether a validated quantitative MRI score of mixed pathology is associated with clinical diagnosis and whether the score differed between ethnicities (Chinese, Malays, and Indians). We then evaluated whether the score was associated with multidomain cognitive impairment and if additional measures of CeVD were further associated with cognitive impairment. We found that lower quantitative MRI scores were associated with severity of clinical diagnosis and Chinese individuals had the highest quantitative MRI scores, followed by Indians and Malays. Lower quantitative MRI scores were also associated with lower performance in attention, language, visuoconstruction, visuomotor, visual, and verbal memory domains. Lastly, the presence of intracranial stenosis and cortical cerebral microinfarcts, but not cerebral microbleeds, were associated with memory performance beyond quantitative MRI scores. Taken together, our results demonstrate the utility of using multiple MRI markers of neurodegeneration and CeVD for identifying multiethnic Asians with the greatest cognitive impairment due to mixed pathology.
    Matched MeSH terms: Memory
  15. Fulltext Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response
    Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.
    Vaccine, 2016 09 14;34(40):4777-86.
    PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028
    Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.
    Matched MeSH terms: Immunologic Memory
  16. Fulltext Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
    Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.
    Nat Commun, 2020 02 10;11(1):821.
    PMID: 32041953 DOI: 10.1038/s41467-020-14442-6
    The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.
    Matched MeSH terms: Immunologic Memory
  17. Fulltext Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion
    Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z
    Sci Rep, 2019 10 10;9(1):14507.
    PMID: 31601902 DOI: 10.1038/s41598-019-50954-y
    Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
    Matched MeSH terms: Spatial Memory/drug effects
  18. Fulltext The modulation of PPARγ1 and PPARγ2 mRNA expression by ciglitazone in CD3/CD28-activated naïve and memory CD4+ T cells
    Norazmi MN, Mohamed R, Nurul AA, Yaacob NS
    Clin. Dev. Immunol., 2012;2012:849195.
    PMID: 22548115 DOI: 10.1155/2012/849195
    Given their roles in immune regulation, the expression of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) 1 and 2 isoforms was investigated in human naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells. Stimulation of both types of cells via the CD3/CD28 pathway resulted in high expression of both PPARγ receptors as measured by real-time PCR. Treatment with the PPARγ agonist, ciglitazone, increased PPARγ1 expression but decreased PPARγ2 expression in stimulated naïve and memory cells. Furthermore, when present, the magnitude of both PPARγ receptors expression was lower in naïve cells, perhaps suggesting a lower regulatory control of these cells. Similar profiles of selected proinflammatory cytokines were expressed by the two cell types following stimulation. The induction of PPARγ1 and suppression of PPARγ2 expressions in naïve and memory CD4+ T cells in the presence of ciglitazone suggest that the PPARγ subtypes may have different roles in the regulation of T-cell function.
    Matched MeSH terms: Immunologic Memory
  19. Fulltext EEG based evaluation of stereoscopic 3D displays for viewer discomfort
    Malik AS, Khairuddin RN, Amin HU, Smith ML, Kamel N, Abdullah JM, et al.
    Biomed Eng Online, 2015;14:21.
    PMID: 25886584 DOI: 10.1186/s12938-015-0006-8
    Consumer preference is rapidly changing from 2D to 3D movies due to the sensational effects of 3D scenes, like those in Avatar and The Hobbit. Two 3D viewing technologies are available: active shutter glasses and passive polarized glasses. However, there are consistent reports of discomfort while viewing in 3D mode where the discomfort may refer to dizziness, headaches, nausea or simply not being able to see in 3D continuously.
    Matched MeSH terms: Memory, Short-Term
  20. Fulltext Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma
    Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA
    BMC Immunol, 2008;9:73.
    PMID: 19087256 DOI: 10.1186/1471-2172-9-73
    BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.
    RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found.
    CONCLUSION: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.
    Matched MeSH terms: Immunologic Memory
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