Abstract
We recently proposed the involvement of diffusible modulators in signalling astrocytes to increase glial cell line-derived neurotrophic factor (GDNF) expression after selective dopaminergic injury by H2O2 or L-DOPA. Here we report that interleukin-1beta (IL-1beta) is involved in this crosstalk between injured neurons and astrocytes. IL-1beta was detected only in the media from challenged neuron-glia cultures. Exogenous IL-1beta did not change GDNF protein levels in astrocyte cultures, and diminished GDNF levels in neuron-glia cultures. This decrease was not due to cell loss, as assessed by the MTT assay and immunocytochemistry. Neither H2O2 nor L-DOPA induced microglia proliferation or appeared to change its activation state. The IL-1 receptor antagonist (IL-1ra) prevented GDNF up-regulation in challenged cultures, showing that IL-1beta is involved in the signalling between injured neurons and astrocytes. Since IL-1ra decreased the number of dopaminergic neurons in H2O2-treated cultures, we propose that IL-1 has a neuroprotective role in this system involving GDNF up-regulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / drug effects
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Blotting, Western
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cells, Cultured
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Dopamine / physiology*
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Dopamine Agents / toxicity
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Enzyme-Linked Immunosorbent Assay
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Glial Cell Line-Derived Neurotrophic Factor / antagonists & inhibitors
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Glial Cell Line-Derived Neurotrophic Factor / biosynthesis*
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Glial Fibrillary Acidic Protein / metabolism
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Hydrogen Peroxide / toxicity
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Immunohistochemistry
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / physiology*
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Levodopa / toxicity
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Mesencephalon / cytology*
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Mesencephalon / physiology*
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Neuroglia / drug effects
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Neuroglia / metabolism
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Oxidants / toxicity
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Rats, Wistar
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Reverse Transcriptase Polymerase Chain Reaction
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Tetrazolium Salts
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Thiazoles
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Up-Regulation / drug effects
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Up-Regulation / physiology
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Ventral Tegmental Area / cytology
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Ventral Tegmental Area / drug effects
Substances
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Dopamine Agents
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Fibrillary Acidic Protein
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Interleukin-1beta
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Oxidants
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RNA, Messenger
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Tetrazolium Salts
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Thiazoles
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Levodopa
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Hydrogen Peroxide
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thiazolyl blue
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Dopamine