Objective: It is known that highly activated microglia and the consequent production of inflammatory cytokines were associated with neuroexcitotoxic injuries. The present study was carried out to explore whether interleukin-1β (IL-1β), a proinflammatory cytokine produced in abundance by activated microglia, mediates increased excitability of hippocampal neurons and the related molecular mechanisms. Methods: Primary cultured microglia were activated by kainic acid (KA), and the KA-treated microglial conditioned medium (KA-MCM) was collected. KA-MCM with or without anti-rat IL-1β monoclonal neutralizing antibody was then injected into the rat in the right cerebral ventricle, or primary cultured hippocampal neurons were treated with the above-mentioned KA-MCM. The population spike amplitude changes in the CA3 region were assessed by electrophysiological recording in vivo. Western blot and RT-PCR assay were performed to investigate the expression changes of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) and inducible nitric oxide synthase (iNOS) expression in hippocampal neurons. Results: Primary cultured microglia were significantly activated by KA with increased IL-1β levels. Interestingly, intracerebroventricular administration of KA-MCM to rats resulted in enhancement of population spike amplitude in the CA3 region and in upregulation of NMDAR1 and iNOS expression in the hippocampus, which was partially attenuated by anti-rat IL-1β antibody. Furthermore, the changes in NMDAR1 and iNOS expression in the rat hippocampus were verified by incubation of primary cultured hippocampal neurons with KA-MCM. Conclusion: This study provides evidence that KA-activated microglia mediate increased excitability of hippocampal neurons in vitro and in vivo and that IL-1β may be one of the main causes of this event.

Keywords:
Microglia, Microglial conditioned medium, Interleukin-1β, Hyperexcitability, Hippocampal neurons, N-methyl-D-aspartate receptor subunit 1, Inducible nitric oxide synthase
This content is only available via PDF.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.