MicroRNA-210-5p Contributes to Cognitive Impairment in Early Vascular Dementia Rat Model Through Targeting Snap25.

Published on Nov 13, 2018in Frontiers in Molecular Neuroscience4.057
· DOI :10.3389/FNMOL.2018.00388
Zhenxing Ren5
Estimated H-index: 5
(Guangzhou University of Chinese Medicine),
Junlong Yu1
Estimated H-index: 1
(Guangzhou University of Chinese Medicine)
+ 6 AuthorsDongfeng Chen22
Estimated H-index: 22
(Guangzhou University of Chinese Medicine)
Vascular dementia (VD) is the most common form of dementia in the elderly. However, little is understood about the role of microRNAs (miRNAs) involved in cognitive impairment in early VD. Here, VD model induced by chronic cerebral ischemia and FBS-free cell model detecting synapse formation were established to investigate the function of microRNAs in early VD. Microarray analysis and real-time reverse transcription PCR showed that miR-210-5p increased significantly in the hippocampus of rat with 4 weeks ischemia. VD model rats also displayed significant cognitive deficits and synaptic loss. Overexpression of miR-210-5p decreased the synaptic number in primary hippocampal neurons. In contrast, specific suppression of miR-210-5p resulted in formation of more synapses. Additionally, intracerebroventricular injection of mir-210-5p agomir to VD rats aggravated phenotypes of cognitive impairment and synaptic loss. These VD-induced phenotypes were effectively attenuated by mir-210 antagomir. Moreover, bioinformatic prediction revealed that Snap25 mRNA is targeted by miR-210-5p. miR-210-5p decreased the luciferase activities of 3’ UTR of Snap25 mRNA. Mutation of predicted miR-210-5p binding sites in the 3’ UTR of Snap25 mRNA abolished the miR-210-5p induced decrease in luciferase activity. Western blot and immunofluorescence staining confirmed that miR-210-5p targets on Snap25. Finally, detected by RT-qPCR and immunofluorescence staining, miR-210-5p agomir downregulated Snap25 expression in CA1 region of VD rats’ hippocampi, in contrast, miR-210-5p antagomir upregulated Snap25 expression. Taken together, miR-210-5p contributes to cognitive impairment in chronic ischemia-induced VD model through regulation of Snap25 expression, which potentially offer the opportunity to develop a new therapeutic strategy for VD.
📖 Papers frequently viewed together
14 Citations
74 Citations
20207.24Aging Cell
12 Authors (Zhongli Shi, ..., Shunjiang Xu)
16 Citations
#1Yang Yao (Tianjin First Center Hospital)H-Index: 4
#2Faqi Wang (TJU: Tianjin University)H-Index: 4
Last. Zhiyun Wang (Tianjin First Center Hospital)H-Index: 2
view all 6 authors...
Abstract The dysfunction of spatial cognition is a character to various neurological disorders and therapeutic strategy. However, it is limited to known risk factors clinically so far. Gastrin releasing peptide (GRP) signaling is a neuropeptide system mediating emotional memory events. However, the effects of GRP agonist on spatial cognition and hippocampal synaptic plasticity are rarely investigated, especially in pathologic condition. This study was designed to investigate the long-term effect...
2 CitationsSource
#1Ning Bao (PRC: China Medical University (PRC))H-Index: 1
#2Bo Fang (PRC: China Medical University (PRC))H-Index: 13
Last. Zhilin Wang (PRC: China Medical University (PRC))H-Index: 4
view all 7 authors...
Ischemia–reperfusion (I/R)-induced spinal cord injury can cause apoptotic damage and subsequently act as a blood–spinal cord barrier damage. MicroRNAs (miRNAs) contributed to the process of I/R injury by regulating their target mRNAs. miR-199a-5p is involved in brain and heart I/R injury; however, its function in the spinal cord is not yet completely clarified. In this study, we investigated the role of miR-199a-5p on spinal cord I/R via the endothelin-converting enzyme 1, especially the apoptos...
30 CitationsSource
microRNAs (miRNAs) have emerged as critical regulators of neuronal dendrite development. Specific precursor (pre-)miRNAs are actively transported to dendrites, but whether this process is regulated by neuronal activity and involved in activity-dependent dendritogenesis is unknown. Here we show that BDNF, a neurotrophin that is released in response to increased neuronal activity, promotes dendritic accumulation of pre-miR-134. Dendritic accumulation, but not transcription of pre-miR-134, is abrog...
14 CitationsSource
#1Wen Zhu (Capital Medical University)H-Index: 10
#2Xue-Rui Wang (Capital Medical University)H-Index: 12
Last. Cun-Zhi Liu (Beijing University of Chinese Medicine)H-Index: 28
view all 8 authors...
Abstract Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to...
20 CitationsSource
#1Ling Wang (TJU: Tianjin University)H-Index: 4
#2Faqi Wang (TJU: Tianjin University)H-Index: 4
Last. Dong Ming (TJU: Tianjin University)H-Index: 24
view all 6 authors...
Abstract Vascular endothelial growth factor (VEGF) has been identified as a potential treatment for effectively improving cognitive function in several neuropathological conditions. However, the underlying mechanism and the relevant downstream protective pathways that are activated in neurons by VEGF remain elusive, especially in chronic global cerebral ischemia. In this study, we intended to investigate the signaling mechanisms of VEGF in cognitive protection and anti-apoptosis in a rat model o...
9 CitationsSource
Objective(s):The major objective of the present study was to investigate the potential neuroprotective effect of berberine chloride on vascular dementia. Berberine, as an ancient medicine in China and India, is the main active component derived from the Berberis sp. Several studies have revealed the beneficial effects of berberine in various neurodegenerative disorders. Materials and Methods: To induce vascular dementia, chronic bilateral common carotid artery occlusion was performed on male Wis...
25 CitationsSource
Summary Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts.
18 CitationsSource
#1Tengfei Zhao (CPU: China Pharmaceutical University)H-Index: 1
#2Yingxue FuH-Index: 1
Last. Xiaoquan Liu (CPU: China Pharmaceutical University)H-Index: 1
view all 4 authors...
: The aim of this study was to examine the comprehensive neuroprotective mechanism of ligustrazine, which is extracted from Ligusticum Chuanxiong Hort., against vascular dementia (VD) in rats and apoptosis in oxygen and glucose deprivation (OGD) PC12 cells. Rats were subjected to bilateral common carotid artery occlusion (BCCAO) surgery and administered ligustrazine intragastrically for 6 weeks. At the end of the experiments, the hippocampal biomarkers brain-derived neurotrophic factor (BDNF), m...
44 CitationsSource
#1Yuqing Liu (GU: Guangzhou University)H-Index: 2
#2Yunjun LiH-Index: 2
Last. Dongfeng Chen (GU: Guangzhou University)H-Index: 22
view all 10 authors...
: Ischemic strokes carry a significant risk of mortality and recurrent vascular events. Recent studies suggest that changes in microRNAs (miRNAs or miRs) may affect the development of the stroke. However, few studies have investigated the role of miRNAs in behavioral disorder in early stroke. In the present study, animal models of middle cerebral artery occlusion (MCAO) are used, as well as a cell model of neurite outgrowth to further investigate the role of miRNAs in targeting synapse-associate...
3 CitationsSource
#1Jun Wang (Soochow University (Suzhou))H-Index: 2
#2Yue-Zhan Zhang (Soochow University (Suzhou))H-Index: 2
Last. Feng Xu (Soochow University (Suzhou))H-Index: 3
view all 3 authors...
: Acute cerebral infarction (ACI) is a common cerebrovascular disease. Previous studies have indicated that microRNAs (miRs) are aberrantly expressed in patients with ACI. However, the functions of miRs in the pathogenesis of ACI still require further investigation. The aim of the present study was to investigate the function of miR-210 in ACI and its associated mechanism. The expression of miR-210 in the serum of 40 patients with ACI and 40 normal controls was examined using reverse transcripti...
11 CitationsSource
Cited By20
#1Dalian Ding (UB: University at Buffalo)H-Index: 57
#2Weidong Qi (Fudan University)H-Index: 4
Last. Richard Salvi (UB: University at Buffalo)H-Index: 80
view all 4 authors...
Abstract null null Excess release of glutamate at the inner hair cell-type I auditory nerve synapse results in excitotoxicity characterized by rapid swelling and disintegration of the afferent synapses, but in some cases, the damage expands to the spiral ganglion soma. Cochlear excitotoxic damage is largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and kainate receptor (KAR) and potentially N-methyl-D-aspartate receptors (NMDAR). Because these receptors a...
Although hippocampal changes due to noise-induced hearing loss have been suggested, little is known about the miRNA levels due to these hippocampal changes. Three-week-old Sprague-Dawley rats were divided into noise and control groups ( null null null null null null null null null null null null null null null null null null null per group). The noise group rats were exposed to white Gaussian noise (115 dB SPL, 4 hours per day) for three days. One day after noise exposure, the hippocampi of rats...
#1Wensi WuH-Index: 1
Last. Zhi Wang (Memorial Hospital of South Bend)
view all 0 authors...
Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioi...
#1Ji Yaoyao (JLU: Jilin University)
#2Lang Xinsong (JLU: Jilin University)
Last. Haiqing Ye (JLU: Jilin University)H-Index: 4
view all 8 authors...
Long-term consumption of a high-fat diet (HFD) can cause glucose and lipid metabolism disorders, damage the brain and nervous system and result in cognitive impairment. The objective of this study was to investigate the preventative effects of Lactobacillus paracasei (Jlus66, a probiotic extracted from cheese in Northeast China) on cognitive impairment associated with HFD. The water maze was used to compare memory changes in mice fed HFD with or without Jlus66. Hippocampal tissue morphology was ...
#2Weihua Yu (CQMU: Chongqing Medical University)H-Index: 7
#4Yang Lü (CQMU: Chongqing Medical University)H-Index: 10
#1Michelle Watts (UQ: University of Queensland)H-Index: 4
#2Gabrielle Williams (Monash University)H-Index: 1
Last. Charles Claudianos (UQ: University of Queensland)H-Index: 34
view all 5 authors...
MicroRNAs are known to be critical regulators of neuronal plasticity. The highly conserved, hypoxia-regulated microRNA-210 (miR-210) has been shown to be associated with long-term memory in invertebrates and dysregulated in neurodevelopmental and neurodegenerative disease models. However, the role of miR-210 in mammalian neuronal function and cognitive behaviour remains unexplored. Here we generated Nestin-cre-driven miR-210 neuronal knockout mice to characterise miR-210 regulation and function ...
1 CitationsSource
#2Valentina Guercio (PHE: Public Health England)H-Index: 2
Last. Seth Love (UoB: University of Bristol)H-Index: 80
view all 6 authors...
Abstract Dementia is arguably the most pressing public health challenge of our age. Since dementia does not have a cure, identifying risk factors that can be controlled has become paramount to reduce the personal, societal and economic burden of dementia. The relationship between exposure to air pollution and effects on cognitive function, cognitive decline and dementia has stimulated increasing scientific interest in the past few years. This review of the literature critically examines the avai...
6 CitationsSource
#1Gozal Bahlakeh (Tabriz University of Medical Sciences)H-Index: 1
#2Ali Gorji (MUMS: Mashhad University of Medical Sciences)H-Index: 33
Last. Tahereh Ghadiri (Tabriz University of Medical Sciences)H-Index: 8
view all 4 authors...
Cognitive dysfunction is a state of losing or having difficulties in remembering, learning, focusing, or making decisions that impact individual healthy life. Small single-stranded and nonprotein coding RNAs, microRNAs (miRNAs) participate actively in regulatory processes, incorporate cognitive signaling pathways, and intensely affect cognitive evolution. miRNAs exert their modification activities through translational or transcriptional processes. Reportedly, cognitive impairment and dementia a...
4 CitationsSource
#1Xiaoxin Wu (CSU: Central South University)H-Index: 5
#2Ross Crawford (QUT: Queensland University of Technology)H-Index: 57
Last. Indira Prasadam (QUT: Queensland University of Technology)H-Index: 22
view all 5 authors...
Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or s...
4 CitationsSource
#1Dolores Siedlecki-Wullich (Autonomous University of Barcelona)H-Index: 1
#2Alfredo J. Miñano-Molina (Autonomous University of Barcelona)H-Index: 10
Last. José Rodríguez-Alvarez (Autonomous University of Barcelona)H-Index: 22
view all 3 authors...
Pathogenic processes underlying Alzheimer’s disease (AD) affect synaptic function from initial asymptomatic stages, long time before the onset of cognitive decline and neurodegeneration. Therefore, reliable biomarkers enabling early AD diagnosis and prognosis are needed to maximize the time window for therapeutic interventions. MicroRNAs (miRNAs) have recently emerged as promising cost-effective and non-invasive biomarkers for AD, since they can be readily detected in different biofluids, includ...
2 CitationsSource