Differential expression of miR-184 in temporal lobe epilepsy patients with and without hippocampal sclerosis - Influence on microglial function.
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.
UCB Pharma S. A., Chemin du Foriest, B - 1420 Braine-l'Alleud, Belgium.
Bénédicte
B
Danis
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Marijke
M
van Rikxoort
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Anita
A
Kretschmann
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Jiong
J
Zhang
Thomson Reuters, IP &Science, 5901 Priestly Dr., #200, Carlsbad, CA 92008, USA.
Patrice
P
Godard
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Lidija
L
Andonovic
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Franziska
F
Siegel
Deptartment of Neuro- / Pathology, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway.
Pitt
P
Niehusmann
UCB Pharma S. A., Chemin du Foriest, B - 1420 Braine-l'Alleud, Belgium.
Etienne
E
Hanon
Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Daniel
D
Delev
Neurosurgery, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
Marec
M
von Lehe
UCB Pharma S. A., Chemin du Foriest, B - 1420 Braine-l'Alleud, Belgium.
Rafal M
RM
Kaminski
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
Alexander
A
Pfeifer
UCB Pharma S. A., Chemin du Foriest, B - 1420 Braine-l'Alleud, Belgium.
Patrik
P
Foerch
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