Expression Patterns of miR-124, miR-134, miR-132, and miR-21 in an Immature Rat Model and Children with Mesial Temporal Lobe Epilepsy
Department of Pediatrics, Xiangya Hospital of Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China. Journal of Molecular Neuroscience
(Impact Factor: 2.34).
01/2013; 50(2). DOI: 10.1007/s12031-013-9953-3
Mesial temporal lobe epilepsy (MTLE) is a particularly devastating form of human epilepsy with significant incidence of medical intractability. MicroRNAs (miRs) are small, noncoding RNAs that regulate the posttranscriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of MTLE development. To study the dynamic expression patterns of brain-specific miR-124 and miR-134 and inflammation-related miR-132 and miR-21, we performed qPCR on the hippocampi of immature rats at 25 days of age. Expressions were monitored in the three stages of MTEL and in the control hippocampal tissues corresponding to the same timeframes. A similar expression method was applied to hippocampi obtained from children with MTLE and normal controls. The expression patterns of miR-124 and miR-134 nearly showed the same dynamics in the three stages of MTLE development. On the other hand, miR-132 and miR-21 showed significant upregulation in acute and chronic stages, while in the latent stage, miR-132 was upregulated and miR-21 was downregulated. The four miRs were upregulated in hippocampal tissues obtained from children with MTLE. The significant upregulation of miR-124 and miR-134 in the seizure-related stages and children suggested that both can be potential targets for anticonvulsant drugs in the epileptic developing brains, while the different expression patterns of miR-132 and miR-21 may suggest different functions in MTLE pathogenesis.
Available from: Ayla Aksoy-Aksel
- "Human temporal lobe epilepsy and experimentally induced epilepsy result in changes of the level of specific miRNAs in brain tissue in a region-and even neural compartment-dependent manner78798081. If one considers different induction protocols, experimental designs and animal species used, then a core set of four epilepsyrelated miRNAs has emerged (miR-132, miR-134, miR-124, miR-34a)82838485. Pilocarpine-induced epilepsy results in increase of hippocampal pri-miR-132and miR-132 level[60,85]. "
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ABSTRACT: MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.
Available from: degruyter.com
- "miRNAs are also involved in the regulation of several aspects of the innate, adaptive immune responses and inflammationrelated disorders. Studies uncovered a subset of miRNAs which are brain-enriched including miRNAs (124, 134, 9, and 138) and inflammationrelated miRNAs including (132, 181a, 221, and 222) which were extensively studied in multiple brain disease in both developing and adult brains    , and also in infectious diseases   . "
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Despite prompt and appropriate care, Streptococcus pneumoniae (S. pneumoniae) meningitis remains a key cause of childhood morbidity and mortality. Recently, several studies suggested the possibility of microRNAs (miRNA) involvement in multiple brain and infectious diseases. This study aimed to investigate the expressional changes of brain-enriched miRNAs (124, 134, 9, and 138), and inflammation-related miRNAs (132, 181a, 221, and 222) in the cerebral cortex of acute S. pneumoniae meningitis in postnatal day 25 rats with and without treatment.
Quantitative polymerase chain reaction (qPCR) was used to measure the expression levels of the tested brain-enriched and inflammation-related miRNAs in the cerebral cortical tissues obtained from acute experimental meningitis rat model induced by intracranial inoculation of S. pneumoniae serotype 3 with and without treatment. Control rats inoculated with saline were also included.
Brainenriched miRNAs are significantly downregulated in untreated animals while after treatment with antibiotic and steroid for 24 hours, miR-124 and miR-9 expressions were nearly equal to the control, while miR-134 and miR-138 were significantly upregulated. Inflammation-related miR-132 was significantly downregulated in untreated and treated animals while miRNAs (181a, 221, and 222) were significantly upregulated in untreated and treated animals.
Acute S. pneumoniae meningitis leads to significant changes in the cerebral cortical expressions of some brain-enriched and inflammation-related miRNAs. These miRNAs may play a role in the pathogenesis of acute bacterial meningitis.
Available from: Cristina Ruedell Reschke
- "Indeed, miRNA responses to seizures often display sharp temporal changes (Sano et al. 2012). Given the independent findings of miR-134 upregulation in the hippocampus of children and adults with TLE (Jimenez- Mateos et al. 2012; Peng et al. 2013), these findings establish increased miR-134 as a conserved molecular response to seizures in the brain. Fig. 6 Reduced clinical seizures and mortality in Ant-134 mice subject to SE. a, b Graphs showing average Racine scores for Scr (n = 11) and Ant-134 (n = 12) animals, a during 90 min after PILO injection and b recorded after lorazepam termination of SE (**P \ 0.01; *P \ 0.05, compared to Scr). "
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ABSTRACT: Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects.
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