Abstract
Temporal lobe epilepsy (TLE) is a chronic neurological disease in humans, which is refractory to pharmacological treatment in about 30% of the patients. Reactive glial cells are thought to play a major role during the development of epilepsy (epileptogenesis) via regulation of brain inflammation and remodeling of the extracellular matrix (ECM). These processes can be regulated by microRNAs (miRs), a class of small non‐coding RNAs, which can control entire gene networks at a post‐transcriptional level. The expression of miRs is known to change dynamically during epileptogenesis. miR‐132 is one of the most commonly upregulated miRs in animal TLE models with important roles shown in neurons. However, the possible role of miR‐132 in glia remains largely unknown. The aim of this study was to characterize the cell‐type specific expression of miR‐132 in the hippocampus of patients with TLE and during epileptogenesis in a rat TLE model. Furthermore, the potential role of miR‐132 was investigated by transfection of human primary cultured astrocytes that were stimulated with the cytokines IL‐1β or TGF‐β1. We showed an increased expression of miR‐132 in the human and rat epileptogenic hippocampus, particularly in glial cells. Transfection of miR‐132 in human primary astrocytes reduced the expression of pro‐epileptogenic COX‐2, IL‐1β, TGF‐β2, CCL2, and MMP3. This suggests that miR‐132, particularly in astrocytes, represents a potential therapeutic target that warrants further in vivo investigation.
Highlights
Epilepsy is a common chronic neurological disease that is estimated to affect more than 65 million people worldwide (WHO [Epilepsy fact sheet], n.d.)
The expression of miR-132 was analyzed in the hippocampus of human and rat brain tissue using two different approaches: the optical density (OD) approach and the in situ reactivity score (IRS) approach
For the in situ reactivity approach, the intensity of the hybridization signal was evaluated in neurons and glia in the dentate gyrus (DG), hilus, and CA1 using a scale of 1–4 (1: no; 2: weak; 3: moderate; 4: strong hybridization signal)
Summary
Epilepsy is a common chronic neurological disease that is estimated to affect more than 65 million people worldwide (WHO [Epilepsy fact sheet], n.d.). Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, which is refractory to pharmacological treatment in about 30% of patients. Neuropathological features associated with TLE include disruption of the blood-brain barrier (BBB), chronic neuroinflammation, gliosis, and remodeling of the extracellular matrix (ECM; Gorter, van Vliet, & Aronica, 2015). Treatments that prevent or modify epileptogenesis in patients do not exist, there is a need for new therapies with anti-epileptogenic and disease-modifying properties (Loscher, Klitgaard, Twyman, & Schmidt, 2013)
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