miR‑134‑5p/Foxp2/Syn1 is involved in cognitive impairment in an early vascular dementia rat model.

Published on Nov 1, 2019in International Journal of Molecular Medicine3.098
· DOI :10.3892/IJMM.2019.4331
Xin Liu2
Estimated H-index: 2
(Guangzhou University of Chinese Medicine),
Ruilin Zhang1
Estimated H-index: 1
(Guangzhou University of Chinese Medicine)
+ 5 AuthorsDongfeng Chen22
Estimated H-index: 22
(Guangzhou University of Chinese Medicine)
: Forkhead box P2 (Foxp2) is a transcription factor involved in vocal learning. However, the number of previous studies that have investigated the role of Foxp2 in early vascular dementia (VD) is limited. The aim of the present study was to determine whether microRNA (miR)‑134‑5p/Foxp2 contributes to cognitive impairment in a chronic ischemia‑induced early VD model. miR‑134‑5p was found to be significantly increased in the cortex in a rat VD model. Intracerebroventricular injection of miR‑134‑5p antagomir into VD rats prevented the loss of synaptic proteins and the development of cognitive impairment phenotypes. Histopathological analysis revealed that miR‑134‑5p aggravated cognitive impairment in VD rats through damage to cortical neurons and loss of synaptic proteins. Bioinformatics analysis predicted that miR‑134‑5p targets Foxp2 mRNA. Dual luciferase analysis and western blotting supported the prediction that miR‑134‑5p targets Foxp2. Furthermore, the silencing of Foxp2 significantly inhibited the effect of miR‑134‑5p on synaptic protein loss. Chromatin immunoprecipitation‑quantitative polymerase chain reaction analysis indicated that Foxp2 binds to the synapsin I (Syn1) promoter at ‑400/‑600 bp upstream of the transcription start site. In conclusion, the miR‑134‑5p/Foxp2/Syn1 axis was found to contribute to cognitive impairment in a chronic ischemia‑induced early VD model, which may enable the development of new therapeutic strategies for the prevention and treatment of VD.
📖 Papers frequently viewed together
15 Citations
16 Citations
27 Citations
#1Xiaoli Niu (Hebei Medical University)H-Index: 2
#2Xin JiangH-Index: 4
Last. Peiyuan Lv (Hebei Medical University)H-Index: 14
view all 9 authors...
BACKGROUND: DL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers. METHODS: Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of...
19 CitationsSource
#1Chunlei LiuH-Index: 2
#1Liu ChunleiH-Index: 2
Last. Min WeihongH-Index: 2
view all 8 authors...
Amelioration of oxidative stress has been the main approach to improve neurodegenerative disorders. In the present study, a walnut peptide with a strong capacity of scavenging reactive oxygen species (ROS) was purified and identified as EVSGPGLSPN by SEC, RP-HPLC, and HPLC-MS/MS. Treatment with EVSGPGLSPN could significantly (P < 0.05) reduce ROS generation, and increase cell viability, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-px) activities in a dose-depen...
12 CitationsSource
#1Thenmoly Damodaran (Universiti Sains Malaysia)H-Index: 4
#2Christian P. Müller (FAU: University of Erlangen-Nuremberg)H-Index: 53
Last. Zurina Hassan (Universiti Sains Malaysia)H-Index: 12
view all 3 authors...
Abstract Background Chronic cerebral hypoperfusion (CCH) can induce the accumulation of reactive oxygen species, which leads to oxidative damage, neuronal injury, and central cholinergic dysfunction in vulnerable regions of the brain, such as the hippocampus and cerebral cortex. These effects can lead to significant cognitive impairments in clinical populations of vascular dementia (VaD). The present studies aimed to investigate the role of the cholinergic system in memory functions and hippocam...
13 CitationsSource
#1Zhenxing Ren (Guangzhou University of Chinese Medicine)H-Index: 5
#2Junlong Yu (Guangzhou University of Chinese Medicine)H-Index: 1
Last. Dongfeng Chen (Guangzhou University of Chinese Medicine)H-Index: 22
view all 9 authors...
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...
17 CitationsSource
#1Jing-Wen Yang (Beijing University of Chinese Medicine)H-Index: 5
#2Xue-Rui Wang (Capital Medical University)H-Index: 12
Last. Cun-Zhi Liu (Beijing University of Chinese Medicine)H-Index: 28
view all 7 authors...
Aims Acupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high‐resolution liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ‐LC‐MS/MS strategy to unravel the underlying mechanism of acupuncture. Methods Wistar rats were subjected to vascular dementia with bilateral common carotid occ...
12 CitationsSource
#1Yuki Higuchi (Monash University Malaysia Campus)H-Index: 3
#2Tomoko Soga (Monash University Malaysia Campus)H-Index: 18
Last. Ishwar S. Parhar (Monash University Malaysia Campus)H-Index: 38
view all 3 authors...
Monoamine oxidase A (MAO-A) is an enzyme that regulates the levels of monoamine neurotransmitters, such as serotonin, noradrenaline and dopamine, and it has been used as a therapeutic target for depression. However, MAO-A inhibitors, which directly acts on MAO-A protein, have limited use due to their adverse effects. MicroRNAs (miRNAs) are 18-22 nucleotide long, small non-coding RNAs, which have recently emerged as regulators of protein levels that could potentially be new therapeutic targets fo...
8 CitationsSource
#1Guo Ll (HMU: Harbin Medical University)H-Index: 1
#2Wang DsH-Index: 1
Last. Cui KgH-Index: 1
view all 4 authors...
OBJECTIVE: Vascular dementia (VD) is a type of memory, cognition, and behavior disorder caused by ischemic stroke or hemorrhagic stroke. It is a common pathogenesis of dementia that is only second to Alzheimer's disease. Inflammation plays a key role in VD. Interleukin-1β (IL-1β) is a kind of pro-inflammatory cytokine, while its mechanism in VD occurrence and development is still unclear. MATERIALS AND METHODS: The healthy male rats were randomly divided into three groups, including sham group, ...
6 CitationsSource
#1Heather McGowan (RU: Rutgers University)H-Index: 7
#2Vincent R. Mirabella (RU: Rutgers University)H-Index: 5
Last. Zhiping P. Pang (RU: Rutgers University)H-Index: 38
view all 9 authors...
Non-coding RNA, including microRNA (miRNA) serves critical regulatory functions in the developing brain. The let-7 family of miRNAs has been shown to regulate neuronal differentiation, neural subtype specification, and synapse formation in animal models. However, the regulatory role of human let-7c (hsa-let-7c) in human neuronal development has yet to be examined. Let-7c is encoded on chromosome 21 in humans and therefore may be overexpressed in human brains in Trisomy 21 (T21), a complex neurod...
8 CitationsSource
#1Sara Busquets Estruch (MPG: Max Planck Society)H-Index: 9
#2Sarah A. Graham (MPG: Max Planck Society)H-Index: 17
Last. Simon E. Fisher (MPG: Max Planck Society)H-Index: 82
view all 10 authors...
textabstractFOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity is regulated. FOXP proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations with other transcription factors might also modulate the functions of FOXP proteins. However, few FOXP-interacting transcription factors have been identified so far. Therefore, we sought to discover additional transcr...
26 CitationsSource
#1Pedro Rodenas-Cuadrado (MPG: Max Planck Society)H-Index: 4
#2Janine Mengede (MPG: Max Planck Society)H-Index: 1
Last. Sonja C. Vernes (MPG: Max Planck Society)H-Index: 24
view all 8 authors...
Genes including FOXP2, FOXP1, and CNTNAP2, have been implicated in human speech and language phenotypes, pointing to a role in the development of normal language-related circuitry in the brain. Although speech and language are unique to humans a comparative approach is possible by addressing language-relevant traits in animal systems. One such trait, vocal learning, represents an essential component of human spoken language, and is shared by cetaceans, pinnipeds, elephants, some birds and bats. ...
14 CitationsSource
Cited By4
#1Satoshi HosokiH-Index: 2
#2Tomotaka TanakaH-Index: 11
Last. Masafumi IharaH-Index: 59
view all 3 authors...
Abstract Reliable quantitative blood biomarkers are important in vascular dementia (VaD) because early diagnosis and therapeutic intervention are effective in preventing progression of dementia. Although many blood biomarkers for acute ischemic stroke (AIS) or VaD have been reported, there are few reliable blood biomarkers. VaD and AIS have similar pathological conditions that are associated with small vessel disease (SVD) such as oxidative stress, inflammation, endothelial dysfunction, and neur...
#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
#1Jing Zhang (University of Pittsburgh)
#2Ping Sun (University of Pittsburgh)H-Index: 9
Last. Ke-Jie Yin (University of Pittsburgh)H-Index: 27
view all 8 authors...
Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post-transcriptional level. As small endogenous non-coding RNAs, microRNAs (miRs) can regulate target gene expression through post-transcriptional ge...
1 CitationsSource
#1Vitale Miceli (ISMETT)H-Index: 10
#2Giovanna Russelli (ISMETT)H-Index: 2
Last. Matteo Bulati (ISMETT)H-Index: 5
view all 9 authors...
Age is the pivotal risk factor for different common medical conditions such as cardiovascular diseases, cancer and dementia. Among age-related disorders, cardiovascular and cerebrovascular diseases, represent the leading causes of premature mortality strictly related to vascular ageing, a pathological condition characterized by endothelial dysfunction, atherosclerosis, hypertension, heart disease and stroke. These features negatively impact on the brain, owing to altered cerebral blood flow, neu...
1 CitationsSource