A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models

作者：Tyzack Giulia E; Hall Claire E; Sibley Christopher R; Cymes Tomasz; Forostyak Serhiy; Carlino Giulia; Meyer Ione F; Schiavo Giampietro; Zhang Su Chun; Gibbons George M; Newcombe Jia; Patani Rickie; Lakatos Andras

来源：Nature Communications, 2017, 8(1): 1164.

DOI：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.

• 出版日期2017-10-27