Abstract
Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE −HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR. We observed that overexpression of miR-184 inhibited cytokine release after LPS stimulation in primary microglial cells, while it did not affect the viability of murine primary neurons and primary astrocytes. Pathway analysis revealed that miR-184 is potentially involved in the regulation of inflammatory signal transduction and apoptosis. Dysregulation of some the potential miR-184 target genes was confirmed by qPCR and 3′UTR luciferase reporter assay. The reduced expression of miR-184 observed in patients with mTLE + HS together with its anti-inflammatory effects indicate that miR-184 might be involved in the modulation of inflammatory processes associated with hippocampal sclerosis which warrants further studies elucidating the role of miR-184 in the pathophysiology of mTLE.
Highlights
Wyler Score IV as definition for severe hippocampal sclerosis (HS)
We identified a decreased expression of miR-184 in Mesial temporal lobe epilepsy (mTLE) +HS patients which might contribute to the chronic inflammatory processes and to a more pronounced neuronal death observed in mTLE +HS patients
HS sclerosis was diagnosed in 14 cases, whereas 10 cases showed no substantial neuronal cell loss in the pyramidal cell layer
Summary
Wyler Score IV as definition for severe HS. Nowadays, HS can be diagnosed using MRI, the typical feature is unilateral volume loss and increased signal intensity on T2-weigthed images[9]. To identify molecular differences between mTLE patients with HS and patients without HS we performed RNA deep sequencing analysis investigating genome-wide miRNA expression patterns in human hippocampal samples resected during surgery from epilepsy patients. To our knowledge, this is the first miRNA sequencing effort comparing mTLE +HS vs mTLE -HS samples. Our aim was to understand if miRNAs contribute to the more pronounced neuronal death or inflammatory responses observed in mTLE +HS patients. We identified a decreased expression of miR-184 in mTLE +HS patients which might contribute to the chronic inflammatory processes and to a more pronounced neuronal death observed in mTLE +HS patients
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