ECTRIMS eLearning

Investigation of remyelination facilitating factors produced by astrocytes in an animal model of multiple sclerosis
Author(s): ,
M Haindl
Affiliations:
Dept. of Neurology, Medical University Graz, Graz
,
U Köck
Affiliations:
Center for Brain Research, Medical University Vienna, Vienna, Austria
,
M Zeitelhofer-Adzemovic
Affiliations:
Dept. of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institute, Stockholm, Sweden
,
M.K Storch
Affiliations:
Dept. of Neurology, Medical University Graz, Graz
,
F Fazekas
Affiliations:
Dept. of Neurology, Medical University Graz, Graz
S Hochmeister
Affiliations:
Dept. of Neurology, Medical University Graz, Graz
ECTRIMS Learn. Hochmeister S. 09/15/16; 146243; P403
Dr. Sonja Hochmeister
Dr. Sonja Hochmeister
Contributions
Abstract

Abstract: P403

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Experimental models

The role of astrocytes in Multiple Sclerosis (MS) is discussed controversially with contradicting data available. Depending on their immediate plaque milieu, astrocytes appear to have functions in driving inflammation as well as in facilitating remyelination through mediators which they produce. BDNF (brain-derived neurotrophic factor) has been suggested to have neuroprotective functions and to promote regeneration of neurons. FGF2 (fibroblast growth factor) is proposed to favour effective remyelination and enhances the recruitment of oligodendrocyte progenitor cells (OGPs). Semaphorin 3A is a guidance molecule, active in controlling OGP cell migration. On the other hand astrocytes are still often believed to act as a barrier for remyelination because of the glial scar (GS) formation.

We investigated the astrocytic reaction in experimental autoimmune encephalomyelitis, induced by active immunization with Myelin Oligodendrocyte Glycoprotein in Dark Agouti rats. This animal model allows examination of lesion evolution over the full course from active demyelination up to a successfully completed repair. We correlated the astroglial reaction by immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) to the remyelination capacity by in situ hybridisation for mRNA of proteolipid protein. Quantitative evaluation and statistical analysis were performed for all lesion stages in a total of over 400 lesions. More than 250 lesions were used for IHC-doublestaining of GFAP and BDNF, FGF2 and SemA respectively.

The amount of GFAP positive astrocytes increased during lesion evolution and reached its peak in shadow plaques. The highest number of OGPs was detected in the state of early remyelination. BDNF and FGF2 reached their peaks in early remyelination with a mean of 15%±5.0 BDNF+ and 17%±5.6 FGF2+ astrocytes. In contrast, SemA+ cells peaked early with 61%±31.3 in active lesions and then decreased with remyelination.

The SemA peak might confirm the relation of SemA OGP guidance with the inflammatory process. BDNF and FGF2 are both closely related with remyelination explaining their presence in early remyelinating lesions. All factors however could be detected in all lesion stages and were even expressed by astrocytes forming a GS. These data support the beneficial role of astrocytes and suggest that even an abundant GS reaction does not prohibit remyelination in this animal model of MS.

Disclosure:

Haindl M: nothing to disclose.

Köck U: nothing to disclose

Zeitelhofer-Adzemovic M: nothing to disclose

Storch MK: nothing to disclose

Fazekas F: nothing to disclose

Hochmeister S: nothing to disclose

We did not receive any specific funding for this work.

Abstract: P403

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Experimental models

The role of astrocytes in Multiple Sclerosis (MS) is discussed controversially with contradicting data available. Depending on their immediate plaque milieu, astrocytes appear to have functions in driving inflammation as well as in facilitating remyelination through mediators which they produce. BDNF (brain-derived neurotrophic factor) has been suggested to have neuroprotective functions and to promote regeneration of neurons. FGF2 (fibroblast growth factor) is proposed to favour effective remyelination and enhances the recruitment of oligodendrocyte progenitor cells (OGPs). Semaphorin 3A is a guidance molecule, active in controlling OGP cell migration. On the other hand astrocytes are still often believed to act as a barrier for remyelination because of the glial scar (GS) formation.

We investigated the astrocytic reaction in experimental autoimmune encephalomyelitis, induced by active immunization with Myelin Oligodendrocyte Glycoprotein in Dark Agouti rats. This animal model allows examination of lesion evolution over the full course from active demyelination up to a successfully completed repair. We correlated the astroglial reaction by immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) to the remyelination capacity by in situ hybridisation for mRNA of proteolipid protein. Quantitative evaluation and statistical analysis were performed for all lesion stages in a total of over 400 lesions. More than 250 lesions were used for IHC-doublestaining of GFAP and BDNF, FGF2 and SemA respectively.

The amount of GFAP positive astrocytes increased during lesion evolution and reached its peak in shadow plaques. The highest number of OGPs was detected in the state of early remyelination. BDNF and FGF2 reached their peaks in early remyelination with a mean of 15%±5.0 BDNF+ and 17%±5.6 FGF2+ astrocytes. In contrast, SemA+ cells peaked early with 61%±31.3 in active lesions and then decreased with remyelination.

The SemA peak might confirm the relation of SemA OGP guidance with the inflammatory process. BDNF and FGF2 are both closely related with remyelination explaining their presence in early remyelinating lesions. All factors however could be detected in all lesion stages and were even expressed by astrocytes forming a GS. These data support the beneficial role of astrocytes and suggest that even an abundant GS reaction does not prohibit remyelination in this animal model of MS.

Disclosure:

Haindl M: nothing to disclose.

Köck U: nothing to disclose

Zeitelhofer-Adzemovic M: nothing to disclose

Storch MK: nothing to disclose

Fazekas F: nothing to disclose

Hochmeister S: nothing to disclose

We did not receive any specific funding for this work.

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