Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury

Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Goeteborg, Västra Götaland, Sweden
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2006; 103(46):17513-8. DOI: 10.1073/pnas.0602841103
Source: PubMed


Reactive astrocytes in neurotrauma, stroke, or neurodegeneration are thought to undergo cellular hypertrophy, based on their morphological appearance revealed by immunohistochemical detection of glial fibrillary acidic protein, vimentin, or nestin, all of them forming intermediate filaments, a part of the cytoskeleton. Here, we used a recently established dye-filling method to reveal the full three-dimensional shape of astrocytes assessing the morphology of reactive astrocytes in two neurotrauma models. Both in the denervated hippocampal region and the lesioned cerebral cortex, reactive astrocytes increased the thickness of their main cellular processes but did not extend to occupy a greater volume of tissue than nonreactive astrocytes. Despite this hypertrophy of glial fibrillary acidic protein-containing cellular processes, interdigitation between adjacent hippocampal astrocytes remained minimal. This work helps to redefine the century-old concept of hypertrophy of reactive astrocytes.

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Available from: Ulrika Wilhelmsson
    • "Astrocytes are interconnected via gap junctions into a large and dynamic network, and in the adult brain astrocytes do not reach into domains of their astrocyte neighbors. The overlap zone between adjacent astrocytes (shown in yellow) reflects only a limited interdigitation of fine cellular processes of adjacent astrocytes Reproduced from [185]. Fig. 2. Astrocytes are highly active cells with many physiological functions; in a pathophysiological context astrocytes become reactive and reactive astrogliosis is a prominent component of a whole range of neurological disorders. "
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    ABSTRACT: Astrocytes maintain the homeostasis of the central nervous system (CNS) by e.g. recycling of neurotransmitters and providing nutrients to neurons. Astrocytes function also as key regulators of synaptic plasticity and adult neurogenesis. Any insult to the CNS tissue triggers a range of molecular, morphological and functional changes of astrocytes jointly called reactive (astro)gliosis. Reactive (astro)gliosis is highly heterogeneous and also context-dependent process that aims at the restoration of homeostasis and limits tissue damage. However, under some circumstances, dysfunctional (astro)gliosis can become detrimental and inhibit adaptive neural plasticity mechanisms needed for functional recovery. Understanding the multifaceted and context-specific functions of astrocytes will contribute to the development of novel therapeutic strategies that, when applied at the right time-point, will improve the outcome of diverse neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
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    • "Reactive astrocytes display an enlarged cell body and processes (Wilhelmsson et al., 2006). In addition, astrocyte arborization is reorganized with reactivity: the number of primary processes changes (Wilhelmsson et al., 2006) or they polarize toward the site of injury (Bardehle et al., 2013) or toward amyloid plaques in AD (see below). Less is known about the thin distal processes in astrocytes called perisynaptic processes (PAP), which contact synapses. "
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    ABSTRACT: Astrocytes play crucial roles in the brain and are involved in the neuroinflammatory response. They become reactive in response to virtually all pathological situations in the brain such as axotomy, ischemia, infection, and neurodegenerative diseases (ND). Astrocyte reactivity was originally characterized by morphological changes (hypertrophy, remodeling of processes) and the overexpression of the intermediate filament glial fibrillary acidic protein (GFAP). However, it is unclear how the normal supportive functions of astrocytes are altered by their reactive state. In ND, in which neuronal dysfunction and astrocyte reactivity take place over several years or decades, the issue is even more complex and highly debated, with several conflicting reports published recently. In this review, we discuss studies addressing the contribution of reactive astrocytes to ND. We describe the molecular triggers leading to astrocyte reactivity during ND, examine how some key astrocyte functions may be enhanced or altered during the disease process, and discuss how astrocyte reactivity may globally affect ND progression. Finally we will consider the anticipated developments in this important field. With this review, we aim to show that the detailed study of reactive astrocytes may open new perspectives for ND.
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    • "Reactive astrogliosis is characterized by hypertrophy of primary processes, a dramatic increase in the expression of intermediate filament proteins such as glial fibrillary acidic protein (GFAP), a decrease in expression of glutamine synthetase [8] [9] [10] and, in some cases, a disruption in domain organization [11]. In addition, we have demonstrated that in the hippocampus (HC), a brain region known to be involved in seizure generation in TLE, there is a dramatic increase in gap junction coupling in reactive astrocytes, glutamate transport becomes more efficient, potassium buffering remains intact [7], and a number of specific subunits of ionotropic kainate receptors (KAR) are found to be expressed in reactive astrocytes soon after kainic acid (KA)-induced SE [12]. "
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