Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission

Microglia are highly sensitive to even small changes in the brain environment, such as invasion of non-hazardous toxicants or the presymptomatic state of diseases. However, the physiological or pathophysiological consequences of their responses remain unknown. Here, we report that cultured microglia sense low concentrations of the neurotoxicant methylmercury (MeHglow) and provide neuroprotection against MeHg, for which astrocytes are also required. When exposed to MeHglow, microglia exocytosed ATP via p38 MAPK- and vesicular nucleotide transporter (VNUT)-dependent mechanisms. Astrocytes responded to the microglia-derived ATP via P2Y1 receptors and released interleukin-6 (IL-6), thereby protecting neurons against MeHglow. These neuroprotective actions were also observed in organotypic hippocampal slices from wild-type mice, but not in slices prepared from VNUT knockout or P2Y1 receptor knockout mice. These findings suggest that microglia sense and respond to even non-hazardous toxicants such as MeHglow and change their phenotype into a neuroprotective one, for which astrocytic support is required.

• Publication year

  2014

• Venue

  Scientific Reports

• Publication date

  2014-03-10

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1038/srep04329PMID 24710318PMCID 3948352
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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