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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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.
Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia 32:1–14PubMedCrossRefGoogle Scholar
Beynon SB, Walker FR (2012) Microglial activation in the injured and healthy brain: what are we really talking about? Practical and theoretical issues associated with the measurement of changes in microglial morphology. Neuroscience 225:162–171. doi:10.1016/j.neuroscience.2012.07.029PubMedCrossRefGoogle Scholar
Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192PubMedGoogle Scholar
Corvetti L, Capsoni S, Cattaneo A, Domenici L (2003) Postnatal development of GFAP in mouse visual cortex is not affected by light deprivation. Glia 41:404–414PubMedCrossRefGoogle Scholar
Cotter DR, Pariante CM, Everall IP (2001) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585–595PubMedCrossRefGoogle Scholar
Czeh B, Simon M, Schmelting B, Hiemke C, Fuchs E (2006) Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology 31:1616–1626. doi:10.1038/sj.npp.1300982PubMedCrossRefGoogle Scholar
Ding DC, Gabbott PL, Totterdell S (2001) Differences in the laminar origin of projections from the medial prefrontal cortex to the nucleus accumbens shell and core regions in the rat. Brain Res 917:81–89PubMedCrossRefGoogle Scholar
Drage MG, Holmes GL, Seyfried TN (2002) Hippocampal neurons and glia in epileptic EL mice. J Neurocytol 31:681–692PubMedCrossRefGoogle Scholar
Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492:145–177. doi:10.1002/cne.20738PubMedCrossRefGoogle Scholar
Goldwater DS, Pavlides C, Hunter RG et al (2009) Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 164:798–808PubMedCrossRefGoogle Scholar
Hinwood M, Morandini J, Day TA, Walker FR (2012) Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex. Cereb Cortex 22:1442–1454. doi:10.1093/cercor/bhr229PubMedCrossRefGoogle Scholar
Hinwood M, Tynan RJ, Charnley JL, Beynon SB, Day TA, Walker FR (2012) Chronic Stress Induced Remodeling of the Prefrontal Cortex: Structural Re-Organization of Microglia and the Inhibitory Effect of Minocycline. Cereb Cortex. doi:10.1093/cercor/bhs151Google Scholar
Hu J, Van Eldik LJ (1996) S100 beta induces apoptotic cell death in cultured astrocytes via a nitric oxide-dependent pathway. Biochim Biophys Acta 1313:239–245PubMedCrossRefGoogle Scholar
Huttunen HJ, Kuja-Panula J, Sorci G, Agneletti AL, Donato R, Rauvala H (2000) Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 275:40096–40105. doi:10.1074/jbc.M006993200PubMedCrossRefGoogle Scholar
Jinno S, Fleischer F, Eckel S, Schmidt V, Kosaka T (2007) Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes. Glia 55:1334–1347PubMedCrossRefGoogle Scholar
Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 95:13290–13295PubMedCrossRefGoogle Scholar
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, WalthamGoogle Scholar
Petzold A, Eikelenboom MJ, Gveric D et al (2002) Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 125:1462–1473PubMedCrossRefGoogle Scholar
Savchenko VL, McKanna JA, Nikonenko IR, Skibo GG (2000) Microglia and astrocytes in the adult rat brain: comparative immunocytochemical analysis demonstrates the efficacy of lipocortin 1 immunoreactivity. Neuroscience 96:195–203PubMedCrossRefGoogle Scholar