Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice

Heterogeneity of glia in different CNS regions may contribute to the selective vulnerability of neuronal populations in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). Here, we explored regional variations in the expression of heat shock protein 25 in glia under conditions...

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Main Authors: Rebecca San Gil, Benjamin E. Clarke, Heath Ecroyd, Bernadett Kalmar, Linda Greensmith
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/5/1257
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author Rebecca San Gil
Benjamin E. Clarke
Heath Ecroyd
Bernadett Kalmar
Linda Greensmith
author_facet Rebecca San Gil
Benjamin E. Clarke
Heath Ecroyd
Bernadett Kalmar
Linda Greensmith
author_sort Rebecca San Gil
collection DOAJ
description Heterogeneity of glia in different CNS regions may contribute to the selective vulnerability of neuronal populations in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). Here, we explored regional variations in the expression of heat shock protein 25 in glia under conditions of acute and chronic stress. Hsp27 (Hsp27; murine orthologue: Hsp25) fulfils a number of cytoprotective functions and may therefore be a possible therapeutic target in ALS. We identified a subpopulation of astrocytes in primary murine mixed glial cultures that expressed Hsp25. Under basal conditions, the proportion of Hsp25-positive astrocytes was twice as high in spinal cord cultures than in cortical cultures. To explore the physiological role of the elevated Hsp25 expression in spinal cord astrocytes, we exposed cortical and spinal cord glia to acute stress, using heat stress and pro-inflammatory stimuli. Surprisingly, we observed no stress-induced increase in Hsp25 expression in either cortical or spinal cord astrocytes. Similarly, exposure to endogenous stress, as modelled in glial cultures from SOD1 <sup>G93A</sup>-ALS mice, did not increase Hsp25 expression above that observed in astrocytes from wild-type mice. In vivo, Hsp25 expression was greater under conditions of chronic stress present in the spinal cord of SOD1 <sup>G93A</sup> mice than in wild-type mice, although this increase in expression is likely to be due to the extensive gliosis that occurs in this model. Together, these results show that there are differences in the expression of Hsp25 in astrocytes in different regions of the central nervous system, but Hsp25 expression is not upregulated under acute or chronic stress conditions.
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spelling doaj.art-79e517f5cee24ee49b3852bffbf260072023-11-21T20:28:42ZengMDPI AGCells2073-44092021-05-01105125710.3390/cells10051257Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> MiceRebecca San Gil0Benjamin E. Clarke1Heath Ecroyd2Bernadett Kalmar3Linda Greensmith4Molecular Horizons and School of Chemistry and Molecular Bioscience, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2519, AustraliaDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UKMolecular Horizons and School of Chemistry and Molecular Bioscience, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2519, AustraliaDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UKDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology, London WC1N 3BG, UKHeterogeneity of glia in different CNS regions may contribute to the selective vulnerability of neuronal populations in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). Here, we explored regional variations in the expression of heat shock protein 25 in glia under conditions of acute and chronic stress. Hsp27 (Hsp27; murine orthologue: Hsp25) fulfils a number of cytoprotective functions and may therefore be a possible therapeutic target in ALS. We identified a subpopulation of astrocytes in primary murine mixed glial cultures that expressed Hsp25. Under basal conditions, the proportion of Hsp25-positive astrocytes was twice as high in spinal cord cultures than in cortical cultures. To explore the physiological role of the elevated Hsp25 expression in spinal cord astrocytes, we exposed cortical and spinal cord glia to acute stress, using heat stress and pro-inflammatory stimuli. Surprisingly, we observed no stress-induced increase in Hsp25 expression in either cortical or spinal cord astrocytes. Similarly, exposure to endogenous stress, as modelled in glial cultures from SOD1 <sup>G93A</sup>-ALS mice, did not increase Hsp25 expression above that observed in astrocytes from wild-type mice. In vivo, Hsp25 expression was greater under conditions of chronic stress present in the spinal cord of SOD1 <sup>G93A</sup> mice than in wild-type mice, although this increase in expression is likely to be due to the extensive gliosis that occurs in this model. Together, these results show that there are differences in the expression of Hsp25 in astrocytes in different regions of the central nervous system, but Hsp25 expression is not upregulated under acute or chronic stress conditions.https://www.mdpi.com/2073-4409/10/5/1257heat shock responseheat shock protein 27gliaastrocytesamyotrophic lateral sclerosismotor neuron disease
spellingShingle Rebecca San Gil
Benjamin E. Clarke
Heath Ecroyd
Bernadett Kalmar
Linda Greensmith
Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
Cells
heat shock response
heat shock protein 27
glia
astrocytes
amyotrophic lateral sclerosis
motor neuron disease
title Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
title_full Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
title_fullStr Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
title_full_unstemmed Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
title_short Regional Differences in Heat Shock Protein 25 Expression in Brain and Spinal Cord Astrocytes of Wild-Type and SOD1 <sup>G93A</sup> Mice
title_sort regional differences in heat shock protein 25 expression in brain and spinal cord astrocytes of wild type and sod1 sup g93a sup mice
topic heat shock response
heat shock protein 27
glia
astrocytes
amyotrophic lateral sclerosis
motor neuron disease
url https://www.mdpi.com/2073-4409/10/5/1257
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