Abstract
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.
Original language | English |
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Article number | 1164 |
Number of pages | 17 |
Journal | Nature Communications |
Volume | 8 |
Issue number | 1 |
DOIs | |
Publication status | Published - 27 Oct 2017 |
Keywords
- amyotrophic lateral sclerosis
- animals
- anti-inflammatory agents
- astrocytes
- axons
- cells
- disease models
- humans
- inflammation
- iInterleukin-6
- male
- mice
- inbred C57BL
- motor neurons
- neurons
- neuroprotection
- receptor
- STAT3 transcription factor
- sciatic nerve
- signal transduction
- transcriptome
- cytology
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Chris Sibley
- School of Biological Sciences - Sir Henry Dale Fellow
- Edinburgh Neuroscience
Person: Academic: Research Active