Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats

Yu-Wen Hung,Yi-Jhan Tseng,Chien-Chen Chou,Yung-Yang Lin,Ming-Tsong Lai

doi:10.1186/1742-2094-10-11

Abstract

BackgroundEpilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE).MethodsSE was induced with pilocarpine in Sprague–Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining.ResultsAfter SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895.ConclusionsAn increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy.

Highlights

Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures
To study the pro-epileptogenic role of monocyte chemoattractant protein-1 (MCP-1) in the seizure-induced aberrant reorganization of the dentate hilus, we evaluated the temporal profiles of MCP-1 expression in the dentate gyrus (DG) after pilocarpine-induced status epilepticus (SE) and determined whether MCP-1 enhances the migration of adult neural progenitors towards ectopic locations
Compared with the Distribution of MCP-1 receptor Chemokine receptor 2 (CCR2) in the hippocampal DG after SE In the DG, CCR2-positive cells were found in the hilus, the subgranular zone (SGZ) and the granule cell layer

Summary

Introduction

Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. Mesial temporal lobe epilepsy (MTLE) is a common type of epilepsy; more than half of patients with MTLE continue to experience seizures despite intensive medical treatment [1]. In some MTLE patients, a medical history-taking reveals an early precipitating brain insult and a following seizure-free latent period before the of epilepsy [6]. The exact mechanisms underlying the epileptogenic structure alterations remain unclear. Previous studies in experimental animals and human patients [5] have suggested a potential contribution of inflammatory process to seizure-related pathologies and the induction of epilepsy [7,8]. Pathological alterations in animal models of epilepsy, such as neuronal cell death, reactive gliosis and neuroplastic changes, might be associated with these neuroinflammatory responses [9]. Neuroinflammation may participate in epileptogenesis [5,7,8,9]

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