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 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.

Zhuyu Annao decoction promotes angiogenesis in mice with cerebral hemorrhage by inhibiting the activity of PHD3

2021 ◽  
pp. 096032712110085
Author(s):  
L Wu ◽  
Y Hu ◽  
L Jiang ◽  
N Liang ◽  
P Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Morris Water Maze ◽  
Cerebral Hemorrhage ◽  
Water Maze ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Therapeutic Effects ◽  
Vascular Endothelial ◽  
Behavioral Experiments

Some traditional Chinese decoctions, such as Zhuyu Annao, exert favorable therapeutic effects on acute cerebral hemorrhage, hemorrhagic stroke, and other neurological diseases, but the underlying mechanism remains unclear. This study aimed to determine whether Zhuyu Annao decoction (ZYAND) protects the injured brain by promoting angiogenesis following intracerebral hemorrhage (ICH) and elucidate its specific mechanism. The effect of ZYAND on the nervous system of mice after ICH was explored through behavioral experiments, such as the Morris water maze and Rotarod tests, and its effects on oxidative stress were explored by detecting several oxidative stress markers, including malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase. Real-time quantitative RT-PCR and WB were used to detect the effects of ZYAND on the levels of prolyl hydroxylase domain 3 (PHD3), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) in the brain tissues of mice. The effect of ZYAND on the NF-κB signaling pathway was detected using a luciferase reporter gene. A human umbilical cord vascular endothelial cell angiogenesis experiment was performed to determine whether ZYAND promotes angiogenesis. The Morris water maze test and other behavioral experiments verified that ZYAND improved the neurobehavior of mice after ICH. ZYAND activated the PHD3/HIF-1α signaling pathway, inhibiting the oxidative damage caused by ICH. In angiogenesis experiments, it was found that ZYAND promoted VEGF-induced angiogenesis by upregulating the expression of HIF-1α, and NF-κB signaling regulated the expression of HIF-1α by inhibiting PHD3. ZYAND exerts a reparative effect on brain tissue damaged after ICH through the NF-κB/ PHD3/HIF-1α/VEGF signaling axis.

scholarly journals Potential protective effect of ovocystatin on aging-related cognitive impairment in rats

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Bartłomiej Stańczykiewicz ◽  
Maria Rutkowska ◽  
Marta Lemieszewska ◽  
Marta Jakubik-Witkowska ◽  
Jakub Gburek ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Morris Water Maze ◽  
Cystatin C ◽  
Cognitive Functions ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Old Rats ◽  
Immunohistochemical Studies

Introduction: Increased occurrence of cognitive deficits in mild cognitive impairment is related with the phenomenon of aging within the population. Cystatin C has been associated with cysteine protease inhibiting properties as well as an induction of autophagy and proliferation that can potentially be used as an adjuvant in the treatment of cognitive decline. The aim of the study was to evaluate the effect of ovocystatin, which is structurally and biologically similar to cystatin C, on cognitive functions in experimental young and aging rat models. Material/Methods: The young (four-month-old) and aging (ten-month-old) Wistar Crl: Wi (Han) rats received ovocystatin (i.p.) for 12 days at a dose of 200 and 20 μg/rat, respectively. Cognitive functions were determined using the Morris water maze. Results: Ovocystatin treatment at a dose of 200 μg/rat improved the performance of old rats in the Morris water maze test via increasing the spent time and the distance traveled in the target zone but the differences were not statistically significant (p>0.05). The results of the study highlight the important role cystatins play in neurodegenerative processes as well as the influence they have on cognitive functions. Furthermore, the obtained findings suggest ovocystatin may be used in the treatment of mild cognitive impairment or cognitive decline in dementia, but further morphological, biochemical and immunohistochemical studies are needed.

MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1

2019 ◽  
Vol 16 (4) ◽  
pp. 382-391
Author(s):  
Jun Xiong ◽  
Huijun Wang ◽  
Feng Mu ◽  
Zhanxue Liu ◽  
Yin Bao ◽  
...  
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Cognitive Impairments ◽  
Luciferase Reporter ◽  
Morris Water Maze Test ◽  
Sevoflurane Anesthesia ◽  
Lim Domain ◽  
Apoptosis And Inflammation ◽  
Hippocampal Apoptosis

Purpose: Research has shown that exposure to anesthesia might increase the risks of cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments remains unclear. Methods: Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected by the Morris water maze (MWM) test. The hippocampus was observed by HE staining. The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase reporter assay. The mRNA and expression levels of related genes and mRNA were examined by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot. Result: Sevoflurane induced the cognitive dysfunction presenting with longer latency time and few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water maze test. At the same time, the expression of LIMK1 was dramatically increased. Conclusion: Altogether, these findings suggested that miR-125b-5p inhibitor could protect against the sevoflurane-induced cognitive impairments by targeting LIMK1.

scholarly journals The Effects ofLoranthus parasiticuson Scopolamine-Induced Memory Impairment in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jin Bae Weon ◽  
Jiwoo Lee ◽  
Min Rye Eom ◽  
Youn Sik Jung ◽  
Choong Je Ma
Keyword(s):  
Passive Avoidance ◽  
Morris Water Maze ◽  
Water Maze ◽  
Ache Activity ◽  
Neuroprotective Effect ◽  
Passive Avoidance Test ◽  
Morris Water Maze Test ◽  
Ht22 Cells ◽  
Enhancing Effect ◽  
Maze Test

This study is undertaken to evaluate cognitive enhancing effect and neuroprotective effect ofLoranthus parasiticus. Cognitive enhancing effect ofLoranthus parasiticuswas investigated on scopolamine-induced amnesia model in Morris water maze test and passive avoidance test. We also examined the neuroprotective effect on glutamate-induced cell death in HT22 cells by MTT assay. These results of Morris water maze test and passive avoidance test indicated that 10 and 50 mg/kg ofLoranthus parasiticusreversed scopolamine-induced memory deficits.Loranthus parasiticusalso protected against glutamate-induced cytotoxicity in HT22 cells. As a result ofin vitrotest for elucidating possible mechanism,Loranthus parasiticusinhibited AChE activity, ROS production, and Ca2+accumulation.Loranthus parasiticusshowed memory enhancing effect and neuroprotective effect and these effects may be related to inhibition of AChE activity, ROS level, and Ca2+influx.

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

2012 ◽  
Vol 30 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Guomin Li ◽  
Xuezhu Zhang ◽  
Haiyan Cheng ◽  
Xuemei Shang ◽  
Hui Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Neuron Loss ◽  
Neuron Density ◽  
Maze Test ◽  
Samp8 Mice

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.

scholarly journals Treadmill Training Improves Cognitive Function via Increasing IGF2 Targeted Downregulation of miRNA-483

2020 ◽  
Author(s):  
Liu-Lin Xiong ◽  
Xiu-Juan Dong ◽  
Lu-Lu Xue ◽  
Jun-Jie Chen ◽  
Mohammed Al-hawwas ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Target Gene ◽  
Treadmill Exercise ◽  
Treadmill Training ◽  
Expression Level ◽  
Morris Water Maze Test ◽  
Maze Test

Abstract Background: Suitable exercise can promote development of cognitive function and improve learning and memory ability of the hippocampus. Nevertheless, mechanisms that elicit these positive effects of exercise are yet needing to be elucidated. IGF2 is known to act as a potent memory and cognitive enhancer, whereas the mechanism by which IGF2 regulates cognitive function related to moderate treadmill exercise remained largely vague.Methods: In the study, rats were subjected to slight, moderate and high intensity treadmill training for 6 weeks. Then, Morris Water maze test was employed to investigate hippocampus-dependent spatial learning and memory ability in rats subjected to different intensity treadmill exercise. Subsequently, the gene chip and Gene Ontology were used for analysis to explore the expression level of IGF2. Furthermore, The TargetScan_7.1, miRDB, and microRNA.org. databases was used to predict the target gene of IGF2. Results: After Morris Water maze test, we found that middle intensity treadmill training could obviously enhance learning and memory function of rats. The qRT-PCR and western blot confirmed that the expression of IGF2 was significantly upregulated in hippocampus after moderate treadmill exercise. Through databases, miRNA-483 was screened and predicted as the target gene of IGF2. Moreover, silencing IGF2 inhibited the neurite growth in the hippocampus of rats, while, miRNA-483-inhibitor ameliorated the silencing IGF2 induced hippocampal neurons impairment to promote the neurite outgrowth.Conclusions: These findings suggested that the treadmill training could enhance the cognitive function, in which the underlying mechanism is involving in elevating the expression level of IGF2 and associated with downregulated miRNA-483. This therefore provide a reliable theoretical explanation on improving cognitive function induced by moderate exercise.

scholarly journals The Effect of Omega-lycotoxin on the Cognitive Impairment Induced by Kainic Acid in Rats

2021 ◽  
Vol 15 (1) ◽  
pp. 49-56
Author(s):  
Ali Hosseini-Sharifabad ◽  
◽  
Mohammad Reza Mofid ◽  
Majid Moradmand ◽  
Mohammad Keimasi ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Passive Avoidance ◽  
Kainic Acid ◽  
Morris Water Maze ◽  
Water Maze ◽  
Pathological Process ◽  
Post Treatment ◽  
Morris Water Maze Test ◽  
Target Area ◽  
Pre Treatment

Background: Excitotoxicity is a common pathological process in neurodegenerative diseases associated with overactivity of N-methyl-D-aspartate (NMDA) and P/Q type voltage-gated calcium (Cav2.1) channels. Omega-lycotoxin-Gsp2671g is a therapeutic tool to modulate overactive Cav2.1 (P/Q type) channels. Omega-lycotoxin binds to Cav2.1 channels with high affinity and selectivity. This study aimed to investigate the effects of Omega-lycotoxin on the cognitive impairment induced by kainic acid in rats. Methods: The effect of pre-treatment and post-treatment trials of intra-hippocampal Cornu Ammonis-3 administration of omega-lycotoxin (0.5, 1 or 2µg) was studied on the cognitive impairment induced by kainic acid in rats. The rats’ learning and memory were assessed by the passive avoidance and a single-day testing version of the Morris water maze method. Results: Omega-lycotoxin caused a significant increase in the latency of the passive avoidance test and the duration of their presence in the target area of the Morris water maze test compared to the groups treated with kainic acid (P<0.0001). There were statistically significant differences for the effects of various doses of omega-lycotoxin. The post-treatment groups showed a greater improvement than those in the pretreatment groups. Conclusion: The findings demonstrated that a single dose of omega-lycotoxin can prevent or revert the memory impairment caused by kainic acid in rats.

scholarly journals Effect of Nyctanthes arbor tristis leaf extract against scopolamine-induced cognitive impairment in rats

2015 ◽  
Vol 60 (4) ◽  
pp. 34-49
Author(s):  
Bashetty Phanindhra ◽  
Akondi Butchi Raju ◽  
Gadiyaram Vikas ◽  
Repala Anusha ◽  
Donapati Deepika
Keyword(s):  
Cognitive Impairment ◽  
Protective Effect ◽  
Morris Water Maze ◽  
Water Maze ◽  
Active Avoidance ◽  
Ethanol Extract ◽  
Thiobarbituric Acid ◽  
Morris Water Maze Test ◽  
Radial Arm Maze ◽  
Maze Test

Summary Nyctanthes arbor tristis (NATE) ethanol extract (150 mg/kg, orally) was evaluated for its protective effect against scopolamine-induced (1 mg/kg i.p.) cognitive impairments in rats using behavioral models like radial arm maze test, Morris water maze test and active avoidance test. NATE effect was evaluated and compared with the standard piracetam (200mg/kg i.p.). NATE (p<0.005) significantly reversed the impairment produced by the scopolamine in radial arm maze test. In addition, NATE also decreased the time period taken to find the hidden platform in Morris water maze test and increased number of avoidances in active avoidance paradigm. Acetylcholinesterase activity and thiobarbituric acid levels were significantly (p<0.005) decreased along with the rise in activities of superoxide dismutase and catalase. This might suggest that the NATE has protective effect against scopolamine-induced cognitive impairment in rats through acetylcholine muscarinic receptor pathway and also antioxidant activity. No significant changes were found in histopathological studies of brain.

Yam (Dioscorea pseudojaponica Yamamoto) Ameliorates Cognition Deficit and Attenuates Oxidative Damage in Senescent Mice Induced by D-Galactose

2009 ◽  
Vol 37 (05) ◽  
pp. 889-902 ◽  
Author(s):  
Chuan-Sung Chiu ◽  
Jeng-Shyan Deng ◽  
Ming-Tsuen Hsieh ◽  
Ming-Jen Fan ◽  
Min-Min Lee ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cognitive Impairment ◽  
Learning And Memory ◽  
Morris Water Maze ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Maze Test ◽  
Mice Brain ◽  
Endogenous Antioxidant

This study attempted to access the neuroprotective effect of yam (Dioscorea pseudojaponica Yamamoto) on the senescent mice induced by D-gal. The mice in the experiments were administered orally with yam (20, 100 or 500 mg/kg for 4 weeks, from the sixth week). The learning and memory abilities of the mice in Morris water maze test and the mechanisms involved in the neuroprotective effect of yam on the mice brain tissue were investigated. The content of diosgenin in the yam was also detected by using HPLC. Mice treated with yam were found to significantly improve their learning and memory abilities in Morris water maze test compared to those treated with D-gal (200 mg/kg for 10 weeks). In addition, yam was also found to increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decrease the malondialdehyde (MDA) level on the brains of D-gal treated mice. Finally, the amount of diosgenin in the yam was 5.49 mg/g extract. To sum up, these results indicate that yam had the potential to be a useful treatment for cognitive impairment in TCM. Its beneficial effect may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

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