Astrocyte to microglia cross-talk in acute and chronic neuroinflammation is shaped by SFRP1

Rueda-Carrasco, J.; Mateo, M. I.; Borroto, A.; Martin-Bermejo, M. J.; Kummer, M. P.; Schwartz, S.; Lopez-Atalaya, J. P.; Alarcon, B.; Heneka, M. T.; Esteve, P.; Bovolenta, P.

doi:10.1101/2020.03.10.982579

bioRxiv · 10.1101/2020.03.10.982579

Astrocyte to microglia cross-talk in acute and chronic neuroinflammation is shaped by SFRP1

Rueda-Carrasco, J.·Mateo, M. I.·Borroto, A.·Martin-Bermejo, M. J.·Kummer, M. P.·Schwartz, S.·Lopez-Atalaya, J. P.·Alarcon, B.·Heneka, M. T.·Esteve, P.·Bovolenta, P.

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Abstract

Neuroinflammation is a common feature of many neurodegenerative diseases, which fosters a dysfunctional neuron-microglia-astrocyte crosstalk that, in turn, maintains microglial cells into a perniciously reactive state that often enhance neuronal damage. The molecular components that mediate this critical communication are however not fully explored. Here, we have asked whether Secreted-Frizzled-Related-Protein-1 (SFRP1), a multifunctional regulator of cell-to-cell communication, is part of the cellular crosstalk underlying neuroinflammation. We show that in mouse models of acute and chronic neuroinflammation, astrocyte-derived SFRP1 is sufficient to promote and sustain microglial activation, and thus a chronic inflammatory state. SFRP1 allows the upregulation of components of Hypoxia Induced Factors-dependent inflammatory pathway and, to a lower extent, of those downstream of the Nuclear Factor-kappaB. We thus propose that SFRP1 acts as a critical astrocyte to microglia amplifier of neuroinflammation, representing a potential valuable therapeutic target for counteracting the harmful effect of chronic inflammation present in several neurodegenerative diseases.

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Rueda-Carrasco, J., Mateo, M. I., Borroto, A., Martin-Bermejo, M. J., Kummer, M. P., Schwartz, S., Lopez-Atalaya, J. P., Alarcon, B., Heneka, M. T., Esteve, P., Bovolenta, P.. 2020-03-11. Astrocyte to microglia cross-talk in acute and chronic neuroinflammation is shaped by SFRP1. https://doi.org/10.1101/2020.03.10.982579

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