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Chronic stress-induced disruption of the astrocyte network is driven by structural atrophy and not loss of astrocytes

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Abstract

Chronic stress is well recognized to decrease the number of GFAP+ astrocytes within the prefrontal cortex (PFC). Recent research, however, has suggested that our understanding of how stress alters astrocytes may be incomplete. Specifically, chronic stress has been shown to induce a unique form of microglial remodelling, but it is not yet clear whether astrocytes also undergo similar structural modifications. Such alterations may be significant given the role of astrocytes in modulating synaptic function. Accordingly, in the current study we have examined changes in astrocyte morphology following exposure to chronic stress in adult rats, using three-dimensional digital reconstructions of astrocytes. Our analysis indicated that chronic stress produced profound atrophy of astrocyte process length, branching and volume. We additionally examined changes in astrocyte-specific S100β, which are both a putative astrocyte marker and a protein whose expression is associated with astrocyte distress. While we found that S100β levels were increased by stress, this increase was not correlated with atrophy. We further established that while chronic stress was associated with a decrease in astrocyte numbers when GFAP labelling was used as a marker, we could find no evidence of a decrease in the total number of cells, based on Nissl staining, or in the number of S100β+ cells. This finding suggests that chronic stress may not actually reduce astrocyte numbers and may instead selectively decrease GFAP expression. The results of the current study are significant as they indicate stress-induced astrocyte-mediated disturbances may not be due to a loss of cells but rather due to significant remodeling of the astrocyte network.

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Acknowledgments

These studies were supported by funding from the Australian National Health and Medical Research Council, the Hunter Medical Research Institute, and the University of Newcastle’s Centre for Translational Neuroscience and Mental Health Research.

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Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW, 2308, Australia

    Ross J. Tynan, Sarah B. Beynon, Madeleine Hinwood, Jason J. Woods & Frederick R. Walker

  2. Centre for Brain and Mental Health Research, University of Newcastle, Newcastle, NSW, Australia

    Ross J. Tynan, Sarah B. Beynon, Madeleine Hinwood, Michael Nilsson, Jason J. Woods & Frederick R. Walker

  3. School of Electrical Engineering and Computer Science, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW, 2308, Australia

    Sarah J. Johnson

  4. Hunter Medical Research Institute, Newcastle, NSW, Australia

    Ross J. Tynan, Sarah B. Beynon, Madeleine Hinwood, Michael Nilsson, Jason J. Woods & Frederick R. Walker

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  1. Ross J. Tynan
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Correspondence to Frederick R. Walker.

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Tynan, R.J., Beynon, S.B., Hinwood, M. et al. Chronic stress-induced disruption of the astrocyte network is driven by structural atrophy and not loss of astrocytes. Acta Neuropathol 126, 75–91 (2013). https://doi.org/10.1007/s00401-013-1102-0

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