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Reduction of lipopolysaccharide-induced neurotoxicity in mouse mixed cortical neuron/glia cultures by ultralow concentrations of dynorphins

  • Original Paper
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Journal of Biomedical Science

Abstract

Previously we reported that ultralow concentrations of dynorphins (10−16 to 10−12 M) inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and proinflammatory cytokines in mouse glia without the participation of κ-opioid receptors. In the current study using mouse cortical neuron-glia cocultures, we examined the possibility that inhibition of glia inflammatory response by dynorphins might be neuroprotective for neurons. LPS, in a concentration-dependent manner, markedly increased the release of lactate dehydrogenase (LDH), an indicator of cellular injury. Ultralow concentrations (10−14 to 10−12 M) of dynorphin (dyn) A-(1–8) significantly prevented the LPS-induced release of LDH, loss of neurons, and changes in cell morphology, in addition to inhibition of LPS-induced nitrite production. Meanwhile, ultralow concentrations (10−15 to 10−13 M) of des-[Tyr1]-dyn A-(2–17), a nonopioid peptide which does not bind to κ-opioid receptors, exhibited the same inhibitory effect as dyn A-(1–17). These results suggest that dynorphins at ultralow concentrations are capable of reducing LPS-induced neuronal injury and these neuroprotective effects of dynorphins are not mediated by classical opioid receptors.

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Authors and Affiliations

  1. Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., USA

    Ling-Yuan Kong, Gwang-Ho Jeohn, Pearlie M. Hudson, Lina Du, Bin Liu & Jau-Shyong Hong

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  1. Ling-Yuan Kong
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  2. Gwang-Ho Jeohn
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Kong, LY., Jeohn, GH., Hudson, P.M. et al. Reduction of lipopolysaccharide-induced neurotoxicity in mouse mixed cortical neuron/glia cultures by ultralow concentrations of dynorphins. J Biomed Sci 7, 241–247 (2000). https://doi.org/10.1007/BF02255472

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