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Neurotoxicity Research

, Volume 5, Issue 6, pp 433–441 | Cite as

The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

  • Ann-Cathrin Radesäter
  • Sara Johansson
  • Caroline Öberg
  • Johan Luthman
Article

Abstract

The neurotoxic effect of the pro-inflammatory cytokine interleukin (IL)-1β was studied in monolayer cultures, obtained using roller-drum incubation of hippocampal slices from neonatal Sprague Dawley rats. Following exposure to recombinant rat IL-1β for four days, a concentration dependent loss was observed in the number of NMDAR1 receptor subunit immunoreactive pyramidal neurons in the cultures, reaching significance at 10 ng/ml rIL-1β. Also incubation with recombinant mouse IL-1β caused a loss of pyramidal neurons, with a significant effect at a concentration of 30 pg/ml. The vitamin E analog trolox (30 μM) was found to exert a protective effect against the rIL-1β-induced neuronal degeneration. A neuroprotective action against rIL-1β was also found after co-incubation with the NMDA antagonist dizocilpine (MK-801; 30 μM), while no protection was found with the GABAA mimetic clomethiazole. Hence, the proinflammatory cytokine IL-1β is neurotoxic to hippocampal pyramidal neurons when studied in anin vitro system with advanced phenotypic characteristics. The neuroprotective effects exerted by trolox and MK-801 suggest that free radicals and NMDA receptor-mediated processes are involved in IL-1β-induced neurodegeneration.

Keywords

Neuroinflammation Cytokines Interleukin-1β Hippocampus Neurodegeneration Organotypic cultures 

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Copyright information

© FP Graham Publishing Co 2003

Authors and Affiliations

  • Ann-Cathrin Radesäter
    • 1
  • Sara Johansson
    • 1
    • 2
  • Caroline Öberg
    • 1
  • Johan Luthman
    • 1
  1. 1.BioscienceLocal Discovery Research Area CNS & Pain ControlSödertäljeSweden
  2. 2.Department of Clinical Neuroscience, Occupational Therapy, and Elderly Care Research (Neurotec)Karolinska InstitutetHuddingeSweden

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