Celsr2‐mediated morphological polarization and functional phenotype of reactive astrocytes in neural repair
Neural repair is highly influenced by reactive astrocytes. Atypical cadherin Celsr2 regulates neuron development and axon regeneration, while its role in glial cells remains unexplored. In this study, we show that Celsr2 is highly expressed in spinal astrocytes of adult mice, and knockout of Celsr2 results in reactive astrocytes with longer protrusions preferentially orientated towards lesion borders in culture scratch assay and injured spinal cord, and elevation of total and active Cdc42 and Rac1 protein in western blots. Inactivation of Celsr2 enhances calcium influx in reactive astrocytes in time‐lapse imaging. Morphological phenotypes of cultured Celsr2−/− astrocytes are rescued by Cdc42 or Rac1 inhibitors. Following spinal cord injury (SCI), Celsr2−/− mice exhibit smaller lesion cavity and glial scar, enhanced fiber regeneration, weaker microglial response, and improved functional recovery than control animals. Similar phenotypes are found in mice with conditional knockout of Celsr2 in astrocytes. In Celsr2−/− mice, astrocyte phenotype is changed and neuroinflammation is alleviated after injury. Inhibiting Cdc42/Rac1 activities compromises astrocyte polarization and the improvement of neural repair and functional recovery in Celsr2−/− mice with SCI. In conclusion, Celsr2 regulates morphological polarization and functional phenotype of reactive astrocytes and inactivating Celsr2 is a potential therapeutic strategy for neural repair.
Other Information
Published in: Glia
License: http://creativecommons.org/licenses/by-nc-nd/4.0/
See article on publisher's website: https://dx.doi.org/10.1002/glia.24378
History
Language
- English
Publisher
WileyPublication Year
- 2023
License statement
This Item is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Institution affiliated with
- Hamad Bin Khalifa University
- College of Health and Life Sciences - HBKU