Epilepsy is a common chronic neurological disease of the brain, affecting more than 65 million people worldwide. Epileptogenesis is the process of the development and further progression of epilepsy. The current pharmacological treatments cannot adequately control seizure activity in about 30% of all epilepsy patients, therefore novel therapeutic approaches, directed at the prevention or modification of epileptogenesis are needed. MicroRNAs (miRNA, miRs) are a class of small non-coding RNAs that are able to control gene expression at the post-transcriptional level. In this thesis we aimed to investigate the involvement of miRNAs in the regulation of key epileptogenic processes in search for new therapeutic targets and miRNA-based approaches for the treatment of acquired epilepsy and associated co-morbidities. We identified the most commonly up-regulated miRNAs in epilepsy and studied their expression and cellular distribution in various epileptogenic pathologies, such as temporal lobe epilepsy (TLE), tuberous sclerosis complex (TSC) and traumatic brain injury (TBI). Furthermore, we investigated these miRNAs in experimental rat models of epileptogenesis and in vitro. The most commonly up-regulated miRNAs during epileptogenesis in the adult brain (miR132, miR142, miR146a and miR155) were found to be involved in the regulation of glial-mediated inflammation and ECM remodelling. In the developing brain miR34a was found to be involved in the regulation of corticogenesis. Our experiments as well as existing pre-clinical and clinical data indicate that miRNAs are able to regulate major processes associated with epileptogenesis. Therefore, modulating miRNAs could be a novel therapeutic approach in the treatment of epilepsy and associated co-morbidities.
|Qualification||Doctor of Philosophy|
|Award date||7 May 2020|
|Publication status||Published - 2020|