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Extracellular histone H1 is neurotoxic and drives a pro-inflammatory response in microglia.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
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2013 (English)In: F1000Research, ISSN 2046-1402, Vol. 2, no 148Article in journal (Refereed) Published
Abstract [en]

In neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B H3 and H4 were not neurotoxic. Innate immunity in the central nervous system is mediated through microglial cells and we show here for the first time that histone H1 promotes their survival, up-regulates MHC class II antigen expression and is a powerful microglial chemoattractant. We propose that when the central nervous system is degenerating, histone H1 drives a positive feedback loop that drives further degeneration and activation of immune defences which can themselves be damaging. We suggest that histone H1 acts as an antimicrobial peptide and kills neurons through mitochondrial damage and apoptosis.

Place, publisher, year, edition, pages
2013. Vol. 2, no 148
National Category
URN: urn:nbn:se:umu:diva-84170DOI: 10.12688/f1000research.2-148.v1PubMedID: 24327882OAI: diva2:679875
Available from: 2013-12-16 Created: 2013-12-16 Last updated: 2014-02-17Bibliographically approved

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Gilthorpe, JonathanOozeer, FazalNash, JuliaCalvo, MargaritaBennett, David LhLumsden, AndrewPini, Adrian
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