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Epilepsy microRNA

Chongyang Tang, Yunhe Gu, Haiyang Wang, Hongmei Wu, Yu Wang, Yao Meng, Zhibin Han, Yifei Gu, Wei Ma, Zhenfeng Jiang, Yuanyuan Song, Meng Na, Dunyue Lu, Zhiguo Lin
OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis...
May 4, 2018: Epilepsy Research
Celine K Vuong, Weizheng Wei, Ji-Ann Lee, Chia-Ho Lin, Andrey Damianov, Luis de la Torre-Ubieta, Reem Halabi, Klara Olofsdotter Otis, Kelsey C Martin, Thomas J O'Dell, Douglas L Black
Dysfunction of the neuronal RNA binding protein RBFOX1 has been linked to epilepsy and autism spectrum disorders. Rbfox1 loss in mice leads to neuronal hyper-excitability and seizures, but the physiological basis for this is unknown. We identify the vSNARE protein Vamp1 as a major Rbfox1 target. Vamp1 is strongly downregulated in Rbfox1 Nes-cKO mice due to loss of 3' UTR binding by RBFOX1. Cytoplasmic Rbfox1 stimulates Vamp1 expression in part by blocking microRNA-9. We find that Vamp1 is specifically expressed in inhibitory neurons, and that both Vamp1 knockdown and Rbfox1 loss lead to decreased inhibitory synaptic transmission and E/I imbalance...
April 4, 2018: Neuron
Michele Simonato
So far, research on epilepsy mechanisms has been designed mainly using animal models and tracking down molecular mechanisms underlying seizures in that model. While this approach is clearly valuable, it can be questioned if it is the best possible. One attractive alternative approach may stem from the consideration of epilepsy as a complex disease of a very complex organ, the brain. This short review summarizes data from analyses of the alterations in expression of microRNAs and their target messenger RNAs in a specific brain subregion, the dentate gyrus of the hippocampus, in three experimental models of lesional epilepsy...
2018: Frontiers in Neurology
Tao-Ran Li, Yan-Jie Jia, Chao Ma, Wen-Ying Qiu, Qun Wang, Xiao-Qiu Shao, Rui-Juan Lv
Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells...
March 23, 2018: Disease Models & Mechanisms
Ya-Bo Feng, You-Ting Lin, Yu-Xiang Han, Yue-Jiu Pang, Jing-Jing Xu, Yuan Xue, Hong Yao
This study aimed to study the protective effect of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective metabotropic glutamate receptor agonist, against hippocampal neuronal apoptosis induced by seizures in a rat model of pilocarpine-induced epilepsy. The Morris water maze test was used to assess the spatial memory abilities of epileptic rats with or without 2R,4R-APDC treatment. TUNEL assay was performed to examine neuronal apoptosis in hippocampus. Western blot was conducted to evaluate changes in the levels of caspase-3 and caspase-9 in hippocampus...
March 2018: Neurochemical Research
Guo-Hua Gong, Feng-Mao An, Yu Wang, Ming Bian, Di Wang, Cheng-Xi Wei
Mesial temporal lobe epilepsy (mTLE), the most common type of temporal lobe epilepsy (TLE), is particularly relevant due to its high frequency of therapeutic resistance of anti-epileptic therapies. MicroRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE. The present study aimed to explore the expression and functions of miRNA-153 in mTLE. The expression levels of miRNA-153 in refractory TLE patients were evaluated...
February 2, 2018: Oncotarget
Patrizia Ambrogini, Maria Cristina Albertini, Michele Betti, Claudia Galati, Davide Lattanzi, David Savelli, Michael Di Palma, Stefania Saccomanno, Desirée Bartolini, Pierangelo Torquato, Gabriele Ruffolo, Fabiola Olivieri, Francesco Galli, Eleonora Palma, Andrea Minelli, Riccardo Cuppini
Seizure-triggered maladaptive neural plasticity and neuroinflammation occur during the latent period as a key underlying event in epilepsy chronicization. Previously, we showed that α-tocopherol (α-T) reduces hippocampal neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)-induced status epilepticus (SE). These findings allowed us to postulate an antiepileptogenic potential for α-T in hippocampal excitotoxicity, in line with clinical evidence showing that α-T improves seizure control in drug-resistant patients...
February 22, 2018: Molecular Neurobiology
Simoni H Avansini, Fábio R Torres, André S Vieira, Danyella B Dogini, Fabio Rogerio, Ana C Coan, Marcia E Morita, Marilisa M Guerreiro, Clarissa L Yasuda, Rodrigo Secolin, Benilton S Carvalho, Murilo G Borges, Vanessa S Almeida, Patrícia A O R Araújo, Luciano Queiroz, Fernando Cendes, Iscia Lopes-Cendes
OBJECTIVE: Focal cortical dysplasias (FCDs) are an important cause of drug-resistant epilepsy. In this work, we aimed to investigate whether abnormal gene regulation, mediated by microRNA, could be involved in FCD type II. METHODS: We used total RNA from the brain tissue of 16 patients with FCD type II and 28 controls. MicroRNA expression was initially assessed by microarray. Quantitative polymerase chain reaction, in situ hybridization, luciferase reporter assays, and deep sequencing for genes in the mTOR pathway were performed to validate and further explore our initial study...
March 2018: Annals of Neurology
Jiaxin Li, Haijun Lin, Zhenrong Sun, Guanyi Kong, Xu Yan, Yujiao Wang, Xiaoxuan Wang, Yanhua Wen, Xiang Liu, Hongkun Zheng, Mei Jia, Zhongfang Shi, Rong Xu, Shaohua Yang, Fang Yuan
BACKGROUND/AIMS: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. METHODS: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients...
2018: Cellular Physiology and Biochemistry
Jackelien van Scheppingen, James D Mills, Till S Zimmer, Diede W M Broekaart, Valentina Iori, Anika Bongaarts, Jasper J Anink, Anand M Iyer, Anatoly Korotkov, Floor E Jansen, Wim van Hecke, Wim G Spliet, Peter C van Rijen, Johannes C Baayen, Annamaria Vezzani, Erwin A van Vliet, Eleonora Aronica
Astrocytes are important mediators of inflammatory processes in the brain and seem to play an important role in several neurological disorders, including epilepsy. Recent studies show that astrocytes produce several microRNAs, which may function as crucial regulators of inflammatory pathways and could be used as therapeutic target. We aim to study which miRNAs are produced by astrocytes during IL-1β mediated inflammatory conditions in vitro, as well as their functional role and to validate these findings in human epileptogenic brain tissue...
May 2018: Glia
Xin Wen, Xin-Rui Han, Yong-Jian Wang, Shan Wang, Min Shen, Zi-Feng Zhang, Shao-Hua Fan, Qun Shan, Liang Wang, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
Epilepsy is a group of neurological disorders characterized by epileptic seizures. In this study, we aim to explore the role of microRNA-421 (miR-421) in hippocampal neurons of epilepsy mice via the TLR/MYD88 pathway. Forty mice were randomly served as the normal and model (established as epilepsy model) groups. Hippocampal neurons were assigned into seven groups with different transfections. The RT-qPCR and western blotting were conducted to examine the expression of miR-421 TLR2, TLR4, MYD88, Bax, Bcl-2, p53, Beclin-1, and LC3II/LC3I...
January 30, 2018: Journal of Cellular Physiology
Yang-Fei Ji, Dan Wang, Yan-Ru Liu, Xing-Rong Ma, Hong Lu, Bo-Ai Zhang
Epilepsy is a common neurological disorder in the central nervous system. Inflammation disrupts the blood-brain barrier (BBB), which is responsible for maintaining brain homeostasis. This study was aimed to investigate the functional role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS stimulation. Inflammatory cell injury was evaluated according to the alterations of cell viability, apoptosis, and expression of inflammatory cytokines...
January 29, 2018: Journal of Cellular Biochemistry
Huilong Zhang, Yun Qu, Aihua Wang
Previous studies have indicated that nuclear factor-κB (NF-κB) has an important role in the pathogenesis of epilepsy. The aim of the present study was to evaluate the expression of microRNA (miRNA)‑146a, phosphorylated (p)‑P65/P65, B‑cell lymphoma‑2(Bcl‑2)/Bcl‑2‑associated X protein (Bax) and pro‑inflammatory cytokines, such as interleukin (IL)‑6, IL‑1β and tumor necrosis factor (TNF‑α) in the brain tissue of rats with epilepsy. Sprague‑Dawley rats were used to establish the epilepsy model using the lithium‑pilocarpine method...
April 2018: Molecular Medicine Reports
Prashant K Srivastava, Paolo Roncon, Katarzyna Lukasiuk, Jan A Gorter, Eleonora Aronica, Asla Pitkänen, Enrico Petretto, Michael R Johnson, Michele Simonato
The identification of mechanisms transforming normal to seizure-generating tissue after brain injury is key to developing new antiepileptogenic treatments. MicroRNAs (miRNAs) may act as regulators and potential treatment targets for epileptogenesis. Here, we undertook a meta-analysis of changes in miRNA expression in the hippocampal dentate gyrus (DG) following an epileptogenic insult in three epilepsy models. We identified 26 miRNAs significantly differentially expressed during epileptogenesis, and five differentially expressed in chronic epilepsy...
November 2017: ENeuro
Yu-Tong Zhang
This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a control group. miR-129, c-Fos, bax and MAPK expressions were detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor + siRNA-c-Fos groups...
November 30, 2017: Journal of Cellular Physiology
Li-Gang Huang, Jing Zou, Qin-Chi Lu
Temporal lobe epilepsy (TLE) is a chronic neurological disease characterized by recurrent spontaneous seizures. MicroRNAs are dysregulated in various pathological conditions including epilepsy. Therefore, we hypothesized that the dysregulation of these microRNAs might also be associated with the pathogenesis of TLE. In this study, we found that a microRNA, hsa-miR-155-5p, was upregulated in patients with TLE post-surgery, and hence associated with clinical and pathological manifestations and seizure outcomes...
November 27, 2017: Brain Research
Xiaofeng Wang, Yifeng Luo, Shuangxi Liu, Liming Tan, Sanhu Wang, Rongyong Man
BACKGROUND: Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. METHODS: microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function...
September 22, 2017: Oncotarget
Shruti Bagla, Daniela Cukovic, Eishi Asano, Sandeep Sood, Aimee Luat, Harry T Chugani, Diane C Chugani, Alan A Dombkowski
Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in various organs and arises due to mutations in the TSC1 or TSC2 genes. TSC mutations lead to a range of neurological manifestations including epilepsy, cognitive impairment, autism spectrum disorders (ASD), and brain lesions that include cortical tubers. There is evidence that seizures arise at or near cortical tubers, but it is unknown why some tubers are epileptogenic while others are not. We have previously reported increased tryptophan metabolism measured with α[11 C]-methyl-l-tryptophan (AMT) positron emission tomography (PET) in epileptogenic tubers in approximately two-thirds of patients with tuberous sclerosis and intractable epilepsy...
January 2018: Neurobiology of Disease
Erwin A van Vliet, Noora Puhakka, James D Mills, Prashant K Srivastava, Michael R Johnson, Paolo Roncon, Shalini Das Gupta, Jenni Karttunen, Michele Simonato, Katarzyna Lukasiuk, Jan A Gorter, Eleonora Aronica, Asla Pitkänen
The World Health Organization estimates that globally 2.4 million people are diagnosed with epilepsy each year. In nearly 30% of these cases, epilepsy cannot be properly controlled by antiepileptic drugs. More importantly, treatments to prevent or modify epileptogenesis do not exist. Therefore, novel therapies are urgently needed. In this respect, it is important to identify which patients will develop epilepsy and which individually tailored treatment is needed. However, currently, we have no tools to identify the patients at risk, and diagnosis of epileptogenesis remains as a major unmet medical need, which relates to lack of diagnostic biomarkers for epileptogenesis...
December 2017: Epilepsia
Jiahang Sun, Xiaoying Gao, Dawei Meng, Yang Xu, Xichun Wang, Xin Gu, Mian Guo, Xiaodong Shao, Hongwen Yan, Chuanlu Jiang, Yongri Zheng
BACKGROUND: MiR-134 is enriched in dendrites of hippocampal neurons and plays crucial roles in the progress of epilepsy. The present study aims to investigate the effects of antagomirs targeting miroRNA-134 (Ant-134) on limk1 expression and the binding of miR-134 and limk1 in experimental seizure. METHODS: Status epilepticus (SE) rat model was established by lithium chloride-pilocarpine injection and was treated with Ant-134 by intracerebroventricular injection...
2017: Cellular Physiology and Biochemistry
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