Abstract:Objective To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats. Methods Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group. Results There was no significant difference in the success rate of induction of SE between the three groups (P > 0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P P P Conclusions The treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.
WU Tian-Hui,YIN Fei,PENG Jing et al. Effect of a microRNA-132 antagonist on pilocarpine-induced status epilepticus in young rats[J]. CJCP, 2016, 18(10): 1030-1034.
Lambert TJ, Storm DR, Sullivan JM. MicroRNA132 modulates short-term synaptic plasticity but not basal release probability in hippocampal neurons[J]. PLoS One, 2010, 5(12): e15182.
[2]
Numakawa T, Richards M, Adachi N, et al. MicroRNA function and neurotrophin BDNF[J]. Neurochem Int, 2011, 59(5): 551-558.
[3]
Henshall DC. microRNAs in the pathophysiology and treatment of status epilepticus[J]. Front Mol Neurosci, 2013, 6: 37.
[4]
Jimenez-Mateos EM, Bray I. miRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132[J]. Am J Pathol, 2011, 179(5): 2519-2532.
[5]
McKiernan RC, Jimenez-Mateos EM, Bray I, et al. Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis[J]. PLoS One, 2012, 7(5): e35921.
[6]
Shaltiel G, Hanan M, Wo l f Y, et al. Hippocampal microRNA-132 mediates stress -inducible cognitive deficits through its acetylcholinesterase target[J]. Brain Struct Funct, 2013, 218(1): 59-72.
[7]
Peng J, Omran A, Ashhab MU, et al. Expression patterns of miR-124, miR-134, microRNA-132, and miR-21 in an immature rat model and children with mesial temporal lobe epilepsy[J]. J Mol Neurosci, 2013, 50(2): 291-297.
[8]
Vo N, Klein ME, Varlamova O, et al. A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis[J]. Proc Natl Acid Sci U S A, 2005, 102(45): 16426-16431.
[9]
Wayman GA, Lee YS, Tokumitsu H, et al. Calmodulin-kinases: modulators of neuronal development and plasticity[J]. Neuron, 2008, 59(6): 914-931.
[10]
Huang Y, Guo J, Wang Q, et al. MicroRNA-132 silencing decreases the spontaneous recurrent seizures[J]. Int J Clin Exp Med, 2014, 7(7): 1639-1649.
Gan N, Yang L, Omran A, et al. Myeloid-related protein 8, an endogenous ligand of Toll-like receptor 4, is involved in epileptogenesis of mesial temporal lobe epilepsy via activation of the nuclear factor-κB pathway in astrocytes[J]. Mol Neurobiol, 2014, 49(1): 337-351.
[13]
Magill ST, Cambronne XA, Luikart BW, et al. microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus[J]. Proc Natl Acad Sci U S A, 2010, 107(47): 20382-20387.
[14]
Luikart BW, Bensen AL, Washburn EK, et al. miR-132 mediates the integration of newborn neurons into the adult dentate gyrus[J]. PLoS One, 2011, 6(5): e19077.
[15]
Guo J, Wang H, Wang Q, et al. Expression of p-CREB and activity-dependent miR-132 in temporal lobe epilepsy[J]. Int J Clin Exp Med, 2014, 7(5): 1297-1306.
[16]
Miller BH, Zeier Z, Xi L, et al. MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function[J]. Proc Natl Acad Sci U S A, 2012, 109(8): 3125-3130.
[17]
Freiman TM, Eismann-Schweimler J, Frotscher M, et al. Granule cell dispersion in temporal lobe epilepsy is associated with changes in dendritic orientation and spine distribution[J]. Exp Neurol, 2011, 229(2): 332-338.
[18]
Hancock ML, Preitner N, Quan J. MicroRNA-132 is enriched in developing axons, locally regulates Rasa1 mRNA, and promotes axon extension[J]. J Neurosci, 2014, 34(1): 66-78.
[19]
Bicker S, Lackinger M, Wei? K, et al. MicroRNA-132, -134, and -138: a microRNA troika rules in neuronal dendrites[J]. Cell Mol Life Sci, 2014, 71(20): 3987-4005.