0481621 - ÚEM 2018 RIV GB eng J - Článek v odborném periodiku
Tyzack, G.E. - Hall, E.C. - Sibley, Ch.R. - Cymes, T. - Forostyak, Serhiy - Carlino, G. - Meyer, I.F. - Schiavo, G. - Zhang, S.Ch. - Gibbons, G.M. - Newcombe, J. - Patani, R. - Lakatos, A.
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Nature Communications. Roč. 8, oct. (2017), s. 1164. ISSN 2041-1723. E-ISSN 2041-1723
Grant CEP: GA ČR(CZ) GA17-21146S
Institucionální podpora: RVO:68378041
Klíčová slova: amyotrophic-lateral-sclerosis * facial motor nucleus * spinal-cord-injury
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 12.353, rok: 2017 ; AIS: 5.685, rok: 2017
DOI: https://doi.org/10.1038/s41467-017-01283-z

Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1-ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.
Trvalý link: http://hdl.handle.net/11104/0277154