Document Type

Article

Publication Date

9-26-2023

Comments

This article is the author's final published version in Experimental Neurology, Volume 370, 2023, Article number 114548.

The published version is available at https://doi.org/10.1016/j.expneurol.2023.114548.

Copyright © 2023 The Authors. Published by Elsevier Inc.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).

Abstract

Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that regulates synaptic maturation, and limits plasticity via GluA2-containing AMPA receptors (AMPARs). It was demonstrated that Chrdl1 expression is very heterogeneous throughout the brain, and it is enriched in astrocytes in cortical layers 2/3, with peak expression in the visual cortex at postnatal day 14. In response to ischemic stroke, Chrdl1 is upregulated during the acute and sub-acute phases in the peri-infarct region, potentially hindering recovery after stroke. Here, we used photothrombosis to model ischemic stroke in the motor cortex of adult male and female mice. In this study, we demonstrate that elimination of Chrdl1 in a global knock-out mouse reduces apoptotic cell death at early post-stroke stages and prevents ischemia-driven synaptic loss of AMPA receptors at later time points, all contributing to faster motor recovery. This suggests that synapse-regulating astrocyte-secreted proteins such as Chrdl1 have therapeutic potential to aid functional recovery after an ischemic injury.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

37769794

Language

English

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