chapter  6
MicroRNAs in Epileptogenesis and Epilepsy
Pages 30

Abstract .................................................................................................................. 154 6.1 Introduction .................................................................................................. 154 6.2 Epilepsy ........................................................................................................ 154

6.2.1 Diagnosis .......................................................................................... 155 6.2.2 Treatment .......................................................................................... 155

6.2.2.1 Nonpharmacological Treatments ....................................... 156 6.3 Mechanisms of Epilepsy ............................................................................... 156

6.3.1 Genetic Mutations ............................................................................. 156 6.3.2 Injury-Induced Epileptogenic Mechanisms ...................................... 157

6.3.2.1 Neuronal Death .................................................................. 157 6.3.2.2 Gliosis ................................................................................ 158 6.3.2.3 Inammation ...................................................................... 159 6.3.2.4 Axonal/Dendritic Reorganization ...................................... 159 6.3.2.5 Extracellular Matrix and Wound Repair ........................... 160

6.3.3 Epigenetic Control of Gene Expression in Epileptogenesis ............. 160 6.4 MicroRNA Biogenesis Pathways in the Brain .............................................. 162

6.4.1 MicroRNA Biogenesis Pathways in Epilepsy ................................... 163 6.4.2 Altered MicroRNA Expression in Epilepsy ..................................... 164 6.4.3 MicroRNA Prole after Status Epileptics: Early Epileptogenic Changes............................................................................................. 165 6.4.4 MicroRNA Prole in Experimental Temporal Lobe Epilepsy ......... 167 6.4.5 MicroRNA Prole in Human Temporal Lobe Epilepsy ................... 167 6.4.6 MicroRNAs Regulating Inammation in Epilepsy: miR-21 and miR-146a .................................................................................... 170 6.4.7 MicroRNAs Implicated in the Regulation of Dendritic Spines

and Neuronal Activity: miR-132, miR-134, and miR-128 ................ 171 6.4.8 MicroRNAs in Seizure-Induced Neuronal Death: miR-34a and miR-184 ...................................................................................... 172

6.5 Conclusions and Future Directions ............................................................... 173 Acknowledgments .................................................................................................. 173 References .............................................................................................................. 173

Epilepsy is the most common serious neurological disease affecting people of all ages. It is characterized by an enduring predisposition to seizures; a result of abnormal, excessive synchronization of neurons. The epileptogenic process features change to multiple signaling pathways including those regulating neuronal morphology and function, gliosis, neuroinammation, and cell death. Recent work has identied select changes to microRNA levels within the hippocampus that may promote or oppose aberrant gene expression during epileptogenesis and in established epilepsy. Functional interrogation has been undertaken using intracerebral delivery of chemically modied antisense oligonucleotides (antagomirs) and genetic techniques. This has demonstrated roles for microRNAs in seizure-induced cell death (miR-34a, miR-184), inammation (miR146a), and neuronal microstructure (miR-128, miR-132, miR-134), in epilepsy. This chapter summarizes work that has characterized microRNA expression in experimental and human epilepsy and the evidence that functional manipulation of microRNAs may be a novel approach to treat or prevent epilepsy.