scholarly journals Inhibition of MicroRNA-96 Ameliorates Cognitive Impairment and Inactivation Autophagy Following Chronic Cerebral Hypoperfusion in the Rat

2018 ◽  
Vol 49 (1) ◽  
pp. 78-86 ◽  
Author(s):  
Peifang Liu ◽  
Peijia Liu ◽  
Zhiyong Wang ◽  
Shaohong Fang ◽  
Yuting Liu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Critical Role ◽  
Beclin 1 ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Vessel Occlusion ◽  
Protein Levels ◽  
Culture Cells ◽  
High Risk Factor ◽  
Underlying Mechanisms

Background/Aims: Chronic cerebral hypoperfusion (CCH) is a high-risk factor for vascular dementia and Alzheimer’s disease. Autophagy plays a critical role in the initiation and progression of CCH. However, the underlying mechanisms remain unclear. In this study, we identified the effect of a microRNA (miR) on autophagy under CCH. Methods: A CCH rat model was established by two-vessel occlusion (2VO). Learning and memory abilities were assessed by the Morris water maze. The protein levels of LC3, beclin-1, and mTOR were detected by western blotting and immunofluorescence assays, miR-96 expression was assessed by real-time PCR, luciferase assays were used to determine the effect of miR-96 on the 3′ untranslated region (UTR) of mTOR, and the number of autophagosomes was examined by electron microscopy. Results: The level of miR-96 was significantly increased in 2VO rats, and inhibition of miR-96 ameliorated the cognitive impairment induced by 2VO. Furthermore, the number of LC3- and beclin-1-positive autophagosomes was increased in 2VO rats, and was decreased after miR-96 antagomir injection. However, the protein level of mTOR was reduced in 2VO rats, and it was down-regulated by miR-96 overexpression and up-regulated by miR-96 inhibition in 2VO rats and primary culture cells. Moreover, the luciferase activity of the 3′-UTR of mTOR was suppressed by miR-96, which was relieved by mutation of the miR-96 binding sites. Conclusion: Our study demonstrated that miR-96 may play a key role in autophagy under CCH by regulating mTOR; therefore, miR-96 may represent a potential therapeutic target for CCH.

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 Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Anil Kumar S ◽  
Saif SA ◽  
Oothuman P ◽  
Mustafa MIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vessel Occlusion

Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), final product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

Therapeutic Benefits of Methylene Blue on Cognitive Impairment during Chronic Cerebral Hypoperfusion

2014 ◽  
Vol 42 (s4) ◽  
pp. S525-S535 ◽  
Author(s):  
Allison Auchter ◽  
Justin Williams ◽  
Bryan Barksdale ◽  
Marie H. Monfils ◽  
Francisco Gonzalez-Lima
Keyword(s):  
Methylene Blue ◽  
Cognitive Impairment ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Therapeutic Benefits

scholarly journals Metformin attenuates sepsis-induced neuronal injury and cognitive impairment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Qin ◽  
Chenliang Zhou ◽  
Xiaochan Xiao ◽  
Cuiping Guo
Keyword(s):  
Cognitive Impairment ◽  
Neuronal Injury ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Morris Water Maze Test ◽  
Biological Technology ◽  
High Risk Factor ◽  
Underlying Mechanisms

Abstract Background Sepsis is considered to be a high-risk factor for cognitive impairment in the brain. The purpose of our study is to explore whether sepsis causes cognitive impairment and try to evaluate the underlying mechanisms and intervention measures. Methods Here, we used cecum ligation and puncture (CLP) to simulate sepsis. Open field, Novel Objective Recognition, and Morris Water Maze Test were used to detect cognitive function, long-term potentiation was used to assess of synaptic plasticity, and molecular biological technics were used to assess synaptic proteins, ELISA kits were used to detect inflammatory factors. Metformin was injected into the lateral ventricle of SD rats, and we evaluated whether metformin alleviated CLP-mediated cognitive impairment using behavioral, electrophysiological and molecular biological technology experiments. Results Here we report hippocampal-dependent cognitive deficits and synaptic dysfunction induced by the CLP, accompanied by a significant increase in inflammatory factors. At the same time, metformin was able to improve cognitive impairment induced by CLP in adult male rats. Conclusion These findings highlight a novel pathogenic mechanism of sepsis-related cognitive impairment through activation of inflammatory factors, and these are blocked by metformin to attenuate sepsis-induced neuronal injury and cognitive impairment.

scholarly journals Tripchlorolide May Improve Spatial Cognition Dysfunction and Synaptic Plasticity after Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhao-Hui Yao ◽  
Xiao-li Yao ◽  
Shao-feng Zhang ◽  
Ji-chang Hu ◽  
Yong Zhang
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Synaptic Proteins ◽  
Cerebral Hypoperfusion ◽  
Spatial Learning And Memory ◽  
Pathophysiological Mechanism

Chronic cerebral hypoperfusion (CCH) is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases. Low cerebral blood flow (CBF) during CCH leads to disturbances in the homeostasis of hemodynamics and energy metabolism, which in turn results in oxidative stress, astroglia overactivation, and synaptic protein downregulation. These events contribute to synaptic plasticity and cognitive dysfunction after CCH. Tripchlorolide (TRC) is an herbal compound with potent neuroprotective effects. The potential of TRC to improve CCH-induced cognitive impairment has not yet been determined. In the current study, we employed behavioral techniques, electrophysiology, Western blotting, immunofluorescence, and Golgi staining to investigate the effect of TRC on spatial learning and memory impairment and on synaptic plasticity changes in rats after CCH. Our findings showed that TRC could rescue CCH-induced spatial learning and memory dysfunction and improve long-term potentiation (LTP) disorders. We also found that TRC could prevent CCH-induced reductions in N-methyl-D-aspartic acid receptor 2B, synapsin I, and postsynaptic density protein 95 levels. Moreover, TRC upregulated cAMP-response element binding protein, which is an important transcription factor for synaptic proteins. TRC also prevented the reduction in dendritic spine density that is caused by CCH. However, sham rats treated with TRC did not show any improvement in cognition. Because CCH causes disturbances in brain energy homeostasis, TRC therapy may resolve this instability by correcting a variety of cognitive-related signaling pathways. However, for the normal brain, TRC treatment led to neither disturbance nor improvement in neural plasticity. Additionally, this treatment neither impaired nor further improved cognition. In conclusion, we found that TRC can improve spatial learning and memory, enhance synaptic plasticity, upregulate the expression of some synaptic proteins, and increase the density of dendritic spines. Our findings suggest that TRC may be beneficial in the treatment of cognitive impairment induced by CCH.

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