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Review
. 2021 May 31;22(11):5904.
doi: 10.3390/ijms22115904.

Astrocytes in Multiple Sclerosis-Essential Constituents with Diverse Multifaceted Functions

Rina Aharoni  1 , Raya Eilam  1 , Ruth Arnon  1
Affiliations
Review

Astrocytes in Multiple Sclerosis-Essential Constituents with Diverse Multifaceted Functions

Rina Aharoni et al. Int J Mol Sci. .

Abstract

In multiple sclerosis (MS), astrocytes respond to the inflammatory stimulation with an early robust process of morphological, transcriptional, biochemical, and functional remodeling. Recent studies utilizing novel technologies in samples from MS patients, and in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), exposed the detrimental and the beneficial, in part contradictory, functions of this heterogeneous cell population. In this review, we summarize the various roles of astrocytes in recruiting immune cells to lesion sites, engendering the inflammatory loop, and inflicting tissue damage. The roles of astrocytes in suppressing excessive inflammation and promoting neuroprotection and repair processes is also discussed. The pivotal roles played by astrocytes make them an attractive therapeutic target. Improved understanding of astrocyte function and diversity, and the mechanisms by which they are regulated may lead to the development of novel approaches to selectively block astrocytic detrimental responses and/or enhance their protective properties.

Keywords: astrocyte activation; astrocytes; blood–brain barrier (BBB); experimental autoimmune encephalomyelitis (EAE); inflammation; multiple sclerosis (MS); neuroprotection; neurotrophic factors; repair processes; tissue damage.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Astrogliosis in the somatosensory cortex of an EAE-induced mouse in comparison to a naïve mouse. Immunohistochemical staining for GFAP, 15 days after EAE-induction.
Figure 2
Figure 2
Astrocyte expression of GM-CSF and its receptor (subunit α) GM-CSFRα. Representative immunohistochemical images from the somatosensory cortex (layer 4). (A) GM-CSF expression and (B) GM-CSFRα expression by GFAP expressing astrocytes in EAE-affected mice, but not in naïve mice. Reprinted with permission from Eilam et al. (2018). Copyright Year 2021, John Wiley and Sons.
Figure 3
Figure 3
Reactive astrocytes detach from the perivascular vicinity and lose the endfeet coverage around the blood vessels (BV). Immunohistochemical depiction of the neurovascular unit in the motor and somatosensory cortex (layer IV). The lumen of the microvessels is visualized by its FITC-dextran content, astrocytes by GFAP expression, neurons by NeuN expression, and overall cell nuclei by Hoechst staining. Representative images from naïve and EAE mice, 21 days after EAE induction. (A) Longitudinal sections along blood vessels and (B) cross sections of penetrating blood vessels. Arrows indicate location of astroglial cell bodies. (C) Quantification of the distances between individual astrocytic cell bodies and their neighboring blood vessels. * p < 0.05. Adapted with permission from ref. [71]. Glia 2018, 66, 1098-1117. Copyright Year 2021, John Wiley and Sons.
Figure 4
Figure 4
Loss of astrocytic confinement to the neuronal boundaries under inflammation. Representative images from layer IV of naïve and EAE mice, 21 days after EAE induction. (A) Left column: dark field illumination of the barrel field area. Middle column: reconstruction of the astrocyte processes performed by manually drawing their branches from GFAP-stained astrocytes. Clear gaps in astrocyte distribution at the barrel boundaries are visible in naïve, but not in EAE mice. Right column: images of astrocytes at high magnification stained with GFAP. (B) Schematic drawing of the barrel field, and an example of lines drawn at the septa centers or the barrel cores. (C) Quantitative analysis of astrocyte processes crossing the line drawing at the septal and barrel cores. * p < 0.001; NS, not significant. Adapted with permission from ref. [71]. Glia 2018, 66, 1098–1117. Copyright Year 2021, John Wiley and Sons.
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References

    1. Reich D.S., Lucchinetti C.F., Calabresi P.A. Multiple sclerosis. N. Engl. J. Med. 2018;378:169–180. doi: 10.1056/NEJMra1401483. - DOI - PMC - PubMed
    1. Lassmann H.J., Van Horssen J., Mahad D. Progressive multiple sclerosis: Pathology and pathogenesis. Nat. Rev. Neurol. 2012;8:647–656. doi: 10.1038/nrneurol.2012.168. - DOI - PubMed
    1. Hohlfeld R., Wekerle H. Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines. Proc. Natl. Acad. Sci. USA. 2004;101:14599–14606. doi: 10.1073/pnas.0404874101. - DOI - PMC - PubMed
    1. Aharoni R. New findings and old controversies in the research of multiple sclerosis and its model experimental autoimmune encephalomyelitis. Expert Rev. Clin. Immunol. 2013;9:423–440. doi: 10.1586/eci.13.21. - DOI - PubMed
    1. Ambucci M., Gargano F., Guerrera G., Battistini L., Borsellino G. One, No One, and One Hundred Thousand: T Regulatory Cells’ Multiple Identities in Neuroimmunity. Front. Immunol. 2019;10:2947. - PMC - PubMed

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