Regulatory microRNAs and vascular cognitive impairment and dementia

Zhang, Jing; Sun, Ping; Zhou, Chao; Zhang, Xintong; Ma, Feifei; Yang, Xu; Hamblin, Milton; Yin, Ke‐Jie

doi:10.1111/cns.13472

Cited by 18 publications

(14 citation statements)

References 140 publications

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“…Recently, specific microRNAs have been believed to be involved in the possible molecular mechanisms and signaling pathways of VCID pathophysiology. 76 Interestingly, previous study have demonstrated that Cx43-medicated GJIC can affect the angiogenesis of tumor via transferring microRNA from endothelial cells to tumor cells. 61 These valuable discoveries can provide another possible research direction for Cx43 in the VCID pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion

Jin

Sun

et al. 2021

J Cereb Blood Flow Metab

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Chronic cerebral hypoperfusion, a major vascular contributor to vascular cognitive impairment and dementia, can exacerbate small vessel pathology. Connexin43, the most abundant gap junction protein in brain tissue, has been found to be critically involved in the pathological changes of vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion. However, the precise mechanisms underpinning its role are unclear. We established a mouse model via bilateral common carotid arteries stenosis on connexin43 heterozygous male mice and demonstrated that connexin43 improves brain blood flow recovery by mediating reparative angiogenesis under chronic cerebral hypoperfusion, which subsequently reduces the characteristic pathologies of vascular cognitive impairment and dementia including white matter lesions and irreversible neuronal injury. We additionally found that connexin43 mediates hypoxia inducible factor-1α expression and then activates the PKA signaling pathway to regulate vascular endothelial growth factor-induced angiogenesis. All the above findings were replicated in bEnd.3 cells treated with 375 µM CoCl2 in vitro. These results suggest that connexin 43 could be instrumental in developing potential therapies for vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion.

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Section: Discussionmentioning

confidence: 99%

Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion

Jin

Sun

et al. 2021

J Cereb Blood Flow Metab

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“…Emerging evidence has suggested the diagnostic and therapeutic values of circulating non-coding RNAs in human diseases, and some excellent articles have reviewed microRNAs, long non-coding RNAs, or circular RNAs as promising non-invasive biomarkers for numerous CNS disorders. For example, microRNAs can be served as diagnostic and prognostic biomarkers of ischemic stroke [ 5 , 38 ], hemorrhagic stroke [ 39 ], traumatic brain injury (TBI) [ 40 ], spinal cord injury (SCI) [ 41 ], glioma [ 42 ], multiple sclerosis (MS) [ 43 ], Alzheimer’s disease (AD) [ 44 ], vascular cognitive impairment and dementia (VCID) [ 45 ], and others. LncRNAs have also been suggested as diagnostic and therapeutic biomarkers for stroke [ 46 ], TBI [ 47 ], SCI [ 48 ], glioma [ 49 ], MS [ 50 ], AD [ 51 ], and other diseases.…”

Section: Non-coding Rnas As Diagnostic and Prognostic Biomarkers For ...mentioning

confidence: 99%

Non-coding RNAs in the regulation of blood–brain barrier functions in central nervous system disorders

Sun

Hamblin

Yin

2022

Fluids Barriers CNS

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The blood–brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of the diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases. Cumulative evidences have demonstrated ncRNA regulation of BBB functions in different CNS diseases. In this review, we have summarized the miRNAs, lncRNAs, and circRNAs that can be served as diagnostic and prognostic biomarkers for BBB injuries, and demonstrated the involvement and underlying mechanisms of ncRNAs in modulating BBB structure and function in various CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), spinal cord injury (SCI), multiple sclerosis (MS), Alzheimer's disease (AD), vascular cognitive impairment and dementia (VCID), brain tumors, brain infections, diabetes, sepsis-associated encephalopathy (SAE), and others. We have also discussed the pharmaceutical drugs that can regulate BBB functions via ncRNAs-related signaling cascades in CNS disorders, along with the challenges, perspective, and therapeutic potential of ncRNA regulation of BBB functions in CNS diseases.

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“…The roles of miRNAs in the pathogenesis of vascular dementia have been widely studied, and further investigations of therapies that target miRNAs are considered important. 23 24 The results of the present study indicated that miR-322-5p was associated with the development of vascular dementia. As previously reported, miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.…”

Section: Discussionmentioning

confidence: 54%

MiR-322-5p Alleviates Cell Injury and Impairment of Cognitive Function in Vascular Dementia by Targeting TSPAN5

et al. 2022

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Purpose As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported that microRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5p has been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatory mechanism of miR-322-5p in vascular dementia. Materials and Methods In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce the model of chronic brain hypoperfusion. Results MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VO rats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpression of TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/R-treated neurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. Conclusion Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. This discovery may provide a potential therapeutic target for dementia.

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Regulatory microRNAs and vascular cognitive impairment and dementia

Cited by 18 publications

References 140 publications

Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion

Connexin43 promotes angiogenesis through activating the HIF-1α/VEGF signaling pathway under chronic cerebral hypoperfusion

Non-coding RNAs in the regulation of blood–brain barrier functions in central nervous system disorders

MiR-322-5p Alleviates Cell Injury and Impairment of Cognitive Function in Vascular Dementia by Targeting TSPAN5

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