scholarly journals Knockdown of lncRNA TUG1 inhibits hippocampal neuronal apoptosis and participates in aerobic exercise-alleviated vascular cognitive impairment

2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Jing Wang ◽  
Yali Niu ◽  
Huaying Tao ◽  
Mina Xue ◽  
Chunxiao Wan
Keyword(s):  
Cognitive Impairment ◽  
Aerobic Exercise ◽  
Cell Apoptosis ◽  
Neuronal Apoptosis ◽  
Molecular Mechanisms ◽  
Glucose Deprivation ◽  
Vascular Cognitive Impairment ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ht22 Cells

Abstract Objectives Our previous study indicated that aerobic exercise relieves cognitive impairment in patients with vascular cognitive impairment (VCI) via regulating brain-derived neurotrophic factor (BDNF), but the mechanism is not yet clear. This study aimed to explore whether lncRNA taurine upregulated gene 1 (TUG1) participates in the process of VCI by regulating BDNF. Methods The expressions of TUG1 and BDNF in the serum of VCI patients were detected. The potential molecular mechanisms of TUG1 in regulating hippocampal neuronal apoptosis were explored in oxygen and glucose deprivation-induced (OGD-induced) hippocampal cell line HT22. The VCI mouse model was established, and TUG1 and BDNF were overexpressed via lentivirus injection. The cognitive impairment of mice was detected by the Morris water maze experiment after the aerobic exercise. Results The level of TUG1 was elevated in the serum of VCI patients compared with the control group. The knockdown of TUG1 in OGD-induced HT22 cells increased BDNF level and decreased cell apoptosis, and the downregulation of BDNF restored the decreased cell apoptosis. RNA immunoprecipitation and RNA pull-down assays showed that TUG1 could bind to BDNF protein. The aerobic exercise alleviated cognitive impairment and inhibited hippocampal apoptosis in VCI mice. Meanwhile, the overexpression of TUG1 reversed the therapeutic effects of aerobic exercise on cognitive impairment. Conclusions The knockdown of TUG1 reduced hippocampal neuronal apoptosis and participates in the aerobic exercise-alleviated VCI, which was partly through regulating BDNF.

scholarly journals Aerobic exercise improves VCI through circRIMS2/miR-186/BDNF-mediated neuronal apoptosis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Yali Niu ◽  
Chunxiao Wan ◽  
Jing Zhang ◽  
Shu Zhang ◽  
Zilong Zhao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Aerobic Exercise ◽  
Morris Water Maze ◽  
Cell Apoptosis ◽  
Water Maze ◽  
Neuronal Apoptosis ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Ht22 Cells

Abstract Background Vascular cognitive impairment (VCI) is a common cognitive disorder caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. Studies have shown that aerobic exercise might alleviate the pathological development of VCI, and our previous study observed that aerobic exercise could alleviate VCI through NF-κB/miR-503/BDNF pathway. However, there are few studies on the mechanism. Therefore, it is of great significance to fill the gaps in the mechanism for the early diagnosis of VCI and the clinical prevention and treatment of vascular dementia. Methods CircRNA microarray analysis and quantitative real-time PCR were used to detect the expression of circRNA regulating synaptic be exocytosis 2 (RIMS2) (circRIMS2). Cell apoptosis was determined by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The dual-luciferase reporter assay was performed to verify the interaction between circRIMS2 and miR-186, as well as miR-186 and BDNF. RNA pull-down assay detected the binding between circRIMS2 and miR-186. A VCI mouse model was established by repeated ligation of bilateral common carotid arteries (2VO). The lentiviral interfering vector was injected into the VCI mice through the lateral ventricle. The mice in the aerobic exercise group performed 30 min (12 m/min) running for 5 days a week. A Morris water maze test was performed after 4 weeks. Results The expression of circRIMS2 and BDNF in the serum of VCI patients was significantly reduced, miR-186 expression was increased, and the expression of circRIMS2 was increased in the 2VO group of mice undergoing aerobic exercise. The expression levels of circRIMS2 and BDNF in the oxygen and glucose deprivation-treated (OGD-treated) cells were decreased, the miR-186 expression and cell apoptosis were increased, while the effect was weakened after transfection with the lentiviral vector pLO-ciR-RIMS2. CircRIMS2 could bind to miR-186, and after interference with circRIMS2 in HT22 cells, the expression of miR-186 was increased. Besides, miR-186 could bind to BDNF, and BDNF expression was decreased because of the overexpression of miR-186 in HT22 cells. The expression level of BDNF in the pLO-ciR-RIMS2 group was increased, and apoptosis was decreased, but the miR-186 mimic weakened the effect of pLO-ciR-RIMS2. Aerobic exercise could shorten the average time that mice reached the platform in the Morris water maze, increase the expression level of circRIMS2 and BDNF, reduce miR-186 expression, and inhibit neuronal apoptosis. However, the interference with circRIMS2 weakened this effect. Conclusion The expression of circRIMS2 was down-regulated in VCI and aerobic exercise reduced neuronal apoptosis, and circRIMS2 improved VCI through the circRIMS2/miR-186/BDNF axis.

scholarly journals Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Xiangli Yan ◽  
Aiming Yu ◽  
Haozhen Zheng ◽  
Shengxin Wang ◽  
Yingying He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Pathological Process ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Positive Effects ◽  
Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

Neurocognitive Plasticity Is Associated with Cardiorespiratory Fitness Following Physical Exercise in Older Adults with Amnestic Mild Cognitive Impairment

2021 ◽  
pp. 1-22
Author(s):  
Galit Yogev-Seligmann ◽  
Tamir Eisenstein ◽  
Elissa Ash ◽  
Nir Giladi ◽  
Haggai Sharon ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Aerobic Exercise ◽  
Cardiorespiratory Fitness ◽  
Neuropsychological Tests ◽  
Aerobic Training ◽  
Amnestic Mild Cognitive Impairment ◽  
Control Group ◽  
Memory Encoding

Background: Aerobic training has been shown to promote structural and functional neurocognitive plasticity in cognitively intact older adults. However, little is known about the neuroplastic potential of aerobic exercise in individuals at risk of Alzheimer’s disease (AD) and dementia. Objective: We aimed to explore the effect of aerobic exercise intervention and cardiorespiratory fitness improvement on brain and cognitive functions in older adults with amnestic mild cognitive impairment (aMCI). Methods: 27 participants with aMCI were randomized to either aerobic training (n = 13) or balance and toning (BAT) control group (n = 14) for a 16-week intervention. Pre- and post-assessments included functional MRI experiments of brain activation during associative memory encoding and neural synchronization during complex information processing, cognitive evaluation using neuropsychological tests, and cardiorespiratory fitness assessment. Results: The aerobic group demonstrated increased frontal activity during memory encoding and increased neural synchronization in higher-order cognitive regions such as the frontal cortex and temporo-parietal junction (TPJ) following the intervention. In contrast, the BAT control group demonstrated decreased brain activity during memory encoding, primarily in occipital, temporal, and parietal areas. Increases in cardiorespiratory fitness were associated with increases in brain activation in both the left inferior frontal and precentral gyri. Furthermore, changes in cardiorespiratory fitness were also correlated with changes in performance on several neuropsychological tests. Conclusion: Aerobic exercise training may result in functional plasticity of high-order cognitive areas, especially, frontal regions, among older adults at risk of AD and dementia. Furthermore, cardiorespiratory fitness may be an important mediating factor of the observed changes in neurocognitive functions.

scholarly journals Dl-3-n-Butylphthalide Alleviates Hippocampal Neuron Damage in Chronic Cerebral Hypoperfusion via Regulation of the CNTF/CNTFRα/JAK2/STAT3 Signaling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxian Li ◽  
Di Wei ◽  
Zheng Zhu ◽  
Xiaomei Xie ◽  
Shuqin Zhan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Signaling Pathways ◽  
Neuronal Death ◽  
Neuronal Apoptosis ◽  
Vascular Cognitive Impairment ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Stat3 Pathway ◽  
Stat3 Signaling

Chronic cerebral hypoperfusion (CCH) contributes to cognitive impairments, and hippocampal neuronal death is one of the key factors involved in this process. Dl-3-n-butylphthalide (D3NB) is a synthetic compound originally isolated from the seeds of Apium graveolens, which exhibits neuroprotective effects against some neurological diseases. However, the protective mechanisms of D3NB in a CCH model mimicking vascular cognitive impairment remains to be explored. We induced CCH in rats by a bilateral common carotid artery occlusion (BCCAO) operation. Animals were randomly divided into a sham-operated group, CCH 4-week group, CCH 8-week group, and the corresponding D3NB-treatment groups. Cultured primary hippocampal neurons were exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic CCH in vitro. We aimed to explore the effects of D3NB treatment on hippocampal neuronal death after CCH as well as its underlying molecular mechanism. We observed memory impairment and increased hippocampal neuronal apoptosis in the CCH groups, combined with inhibition of CNTF/CNTFRα/JAK2/STAT3 signaling, as compared with that of sham control rats. D3NB significantly attenuated cognitive impairment in CCH rats and decreased hippocampal neuronal apoptosis after BCCAO in vivo or OGD/R in vitro. More importantly, D3NB reversed the inhibition of CNTF/CNTFRα expression and activated the JAK2/STAT3 pathway. Additionally, JAK2/STAT3 pathway inhibitor AG490 counteracted the protective effects of D3NB in vitro. Our results suggest that D3NB could improve cognitive function after CCH and that this neuroprotective effect may be associated with reduced hippocampal neuronal apoptosis via modulation of CNTF/CNTFRα/JAK2/STAT3 signaling pathways. D3NB may be a promising therapeutic strategy for vascular cognitive impairment induced by CCH.

scholarly journals PO-221 Effects of different motor functional therapies on cognitive impairment in type 2 diabetes mellitus

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Yu Zhou
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Cognitive Impairment ◽  
Oxygen Uptake ◽  
Elderly Patients ◽  
Resistance Exercise ◽  
Aerobic Exercise ◽  
Exercise Group ◽  
Control Group

Objective The clinical manifestations of diabetic cognitive dysfunction are decreased visual spatial ability, executive dysfunction, mental activity speed and attention, and decreased abstract logical reasoning. Cognitive dysfunction is irreversible. Timely and accurate assessment and diagnosis, early detection and intervention to delay disease progression are particularly critical. The Cognitive Assessment Scale plays an important role in screening for cognitive dysfunction in diabetes. To observe the effects of motor functional therapy on cognitive impairment and blood glucose, blood lipids, body weight, body composition, and maximal oxygen uptake in patients with type 2 diabetes. Methods A total of 63 elderly patients with type 2 diabetes mellitus in Chengdu community aged ≥65 years and educated for ≥12 years were enrolled in the motor function therapy group according to the simple mental state examination (MMSE) score (diabetes cognitive impairment, MMSE total score) ≥ 20 points, aerobic exercise group, n = 21) and functional function therapy group (diabetes cognitive impairment, MMSE total score ≥ 20 points, resistance exercise group, n = 21). The adult community of diabetes in Chengdu (normal cognitive function) with age ≥ 65 years, education time ≥ 12 years, and MMSE total score ≥ 24 points was used as the control group (n=21). Montreal Cognitive Assessment Scale (MOCA): MOCA is an assessment tool developed by Nasreddine and clinically proven to be used for rapid screening of MCI. There were no statistical differences in baseline data (age, gender, and hypertension incidence) among the 3 groups of patients. The LOTCA scale was used to evaluate the cognitive function of the subjects and to compare between groups. Sixty-three patients with type 2 diabetes were randomly divided into aerobic exercise intensity group (50% VO2max) (n=21), resistance exercise intensity group and control group (n=21). Both the aerobic exercise group and the resistance exercise group underwent a 12-week moderate-intensity exercise three times a week. The resistance middle strength group was trained 2 groups each time, each group was 25 minutes, the group rested for 5 minutes, 55 minutes in total, and the aerobic medium intensity group continued to exercise for 55 minutes. All patients underwent fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), body weight, and fat weight (FW) before and after training. , lean body mass (LBM), maximal oxygen uptake (VO2max) determination; measure the energy expenditure of word movement and the total energy expenditure of the entire exercise process. Results There were no significant differences among the three groups before the test (P>0.05). All the indexes of the medium-intensity resistance exercise group and the medium-intensity aerobic exercise group were significantly different from the control group (P<0.05). After the MOCA score test There was an improvement in the score before the trial, and the total score of LOTCA was significantly different among the three groups. In addition to perceptual sub-items (item identification), the aerobic exercise group and the resistance exercise group LOTCA scale in perceptual sub-projects (incomplete object recognition), visual motion organization and its sub-projects (copying two-dimensional graphics, building blocks) The design and puzzle) project scores were higher than before the test, close to the control group score. The scores of the two groups of exercise therapy in the thinking operation and its sub-projects (Riska organized shape classification, picture arrangement B and geometric reasoning) and attention-focused items were lower than the control group. Compared with the resistance exercise, there was a significant difference in the maximum oxygen uptake between aerobic exercise and resistance exercise (P<0.05). Compared with the total exercise energy consumption in the first 6 weeks, the aerobic exercise group was superior to the resistance exercise group. The total exercise energy expenditure was compared in the last 6 weeks, and the resistance exercise group was superior to the aerobic exercise group. Conclusions Elderly patients with type 2 diabetes may have cognitive impairment earlier. In the absence of differences in exercise, the aerobic exercise group and the resistance exercise group improve cognitive impairment, blood sugar, blood fat, body weight, and body composition in patients with type 2 diabetes. There is no significant difference. Compared with MMSE, LOTCA has the advantage of identifying early cognitive impairment in elderly patients with type 2 diabetes and distinguishing the severity of the damage.  

scholarly journals Cardiovascular risk moderates the effect of aerobic exercise on executive functions in older adults with subcortical ischemic vascular cognitive impairment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cindy K. Barha ◽  
Elizabeth Dao ◽  
Lauren Marcotte ◽  
Ging-Yuek Robin Hsiung ◽  
Roger Tam ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Executive Functions ◽  
Aerobic Exercise ◽  
Digit Span ◽  
Vascular Cognitive Impairment ◽  
Analysis Of Covariance ◽  
Trail Making Test ◽  
Executive Processes ◽  
Trail Making

AbstractAerobic training (AT) can promote cognitive function in adults with Subcortical Ischemic Vascular Cognitive Impairment (SIVCI) by modifying cardiovascular risk factors. However, pre-existing cardiovascular health may attenuate the benefits of AT on cognitive outcomes in SIVCI. We examined whether baseline cardiovascular risk moderates the effect of a 6-month progressive AT program on executive functions with a secondary analysis of a randomized controlled trial in 71 adults, who were randomized to either: (1) 3×/week progressive AT; or (2) education program (CON). Three executive processes were measured: (1) response inhibition by Stroop Test; (2) working memory by digits backward test; and (3) set shifting by the Trail Making Test. Baseline cardiovascular risk was calculated using the Framingham cardiovascular disease (CVD) Risk Score (FCRS), and participants were classified as either low risk (< 20% FCRS score; LCVR) or high risk (≥ 20% FCRS score; HCVR). A complete case analysis (n = 58) was conducted using an analysis of covariance (ANCOVA) to evaluate between-group differences in the three executive processes. A significant interaction was found between cardiovascular risk group and intervention group (AT or CON) for the digit span backward and the Trail Making Test. AT improved performance compared with CON in those with LCVR, while in those with HCVR, AT did not improve performance compared with CON. Baseline cardiovascular risk significantly moderates the efficacy of AT on cognition. Our findings highlight the importance of intervening early in the disease course of SIVCI, when cardiovascular risk may be lower, to reap maximum benefits of aerobic exercise.

scholarly journals MEG3 inhibits proliferation and promote apoptosis in osteoarthritis chondrocytes by miR-361-5p/wnt/β-catenin axis

2019 ◽  
Author(s):  
Anying Wang ◽  
Naixia Hu ◽  
Yefeng Zhang ◽  
Yuanzhen Chen ◽  
Changhui Su ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Control Group ◽  
Oa Chondrocytes ◽  
Inhibit Cell Proliferation

Abstract Background: This study aimed to investigate the role of long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) and related molecular mechanisms in osteoarthritis (OA). Methods: Patients with OA and patients undergoing thigh amputation were involved in OA group and control group, respectively. Cartilage tissues of all patients were isolated and cultured. Based on different transfection, MEG3 cells were grouped into Blank, pcDNA3.1-NC, pcDNA3.1-MEG3, si-NC, si-MEG3, pcDNA3.1-NC + mimics NC, pcDNA3.1-MEG3 + mimics NC, pcDNA3.1-NC + miR-361-5p mimics and pcDNA3.1-MEG3 + miR-361-5p mimics group. The cells transfected with pcDNA3.1-NC and pcDNA3.1-MEG3, and then cultured with XAV939 was named as pcDNA3.1-NC +XAV939 group and pcDNA3.1-MEG3 + XAV939 group respectively. The RT-qPCR was used to detect the expression of MEG3 and miR-361-5p. Moreover, Western blot, luciferase reporter assay, RIP, CCK-8 and flow cytometry analysis were performed to reveal the morphology, proliferation and apoptosis in cartilage cells. Finally, the histological analysis and immunostaining were performed on OA rat model. Results: The expression of lncRNA MEG3 and miR-361-5p in OA was significantly decreased and increased respectively than that in normal. Meanwhile, MEG3 was competitive binding with miR-361-5p in OA chondrocytes. Moreover, the Western blot and CCK-8 assay showed that MEG3 might inhibit cell proliferation and promote cell apoptosis via Wnt/β-catenin pathway. Finally, rat model analysis showed that MEG3 contributed to the cartilage matrix degradation. Conclusion: MEG3 and miR-361-5p might down-regulated and up-regulated respectively in the chondrocytes of OA patients. Furthermore, MEG3 might inhibit cell proliferation and promote cell apoptosis via miR-361-5p/Wnt/β-catenin axis in OA chondrocytes.

scholarly journals The aging venous system: from varicosities to vascular cognitive impairment

GeroScience ◽  
2021 ◽  
Author(s):  
Andrea Ágnes Molnár ◽  
György László Nádasy ◽  
Gabriella Dörnyei ◽  
Bernadett Bettina Patai ◽  
Jordan Delfavero ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Molecular Mechanisms ◽  
Varicose Veins ◽  
Critical Role ◽  
Vascular Cognitive Impairment ◽  
Venous System ◽  
Potential Contribution ◽  
Age Related ◽  
Venous Diseases

Abstract Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

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