Limits...
Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis.

Amir-Levy Y, Mausner-Fainberg K, Karni A - Mult Scler Int (2014)

Bottom Line: Methods.No immunosuppressive effect was found.Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv 64239, Israel.

ABSTRACT
Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU(+)GFAP(+) NSCs to BrdU(+)DCX(+) neuroblasts in the subventricular zone (SVZ), increased BrdU(+)NeuN(+) neurons in the granular cell layer of the dentate gyrus, and increased BrdU(+)O4(+) oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.

No MeSH data available.


Related in: MedlinePlus

Increased numbers of de novo oligodendrocytes in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+O4+ cells in the SGZ and SVZ of IC-treated mice (a and d, resp.) and of anti-EGF Ab-treated mice (b and e, resp.) on day 18 after immunization. Quantification of %BrdU+O4+ cells in the SGZ and in the SVZ (c and f, correspondingly) revealed a nonsignificant trend for induction of BrdU+O4+ in the SGZ, along with a significant induction in BrdU+O4+ cells in the SVZ. Images were obtained using a confocal microscopy, coronal sections. Quantification was performed using ZEN 2011 software on 3 sections from each mouse (3 mice from each group, total n = 9). DG, dentate gyrus, LV, lateral ventricle, SVZ, subventricular zone, and cc, corpus callosum. Scale bar: 10 μm (magnification = ×63).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4295609&req=5

fig4: Increased numbers of de novo oligodendrocytes in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+O4+ cells in the SGZ and SVZ of IC-treated mice (a and d, resp.) and of anti-EGF Ab-treated mice (b and e, resp.) on day 18 after immunization. Quantification of %BrdU+O4+ cells in the SGZ and in the SVZ (c and f, correspondingly) revealed a nonsignificant trend for induction of BrdU+O4+ in the SGZ, along with a significant induction in BrdU+O4+ cells in the SVZ. Images were obtained using a confocal microscopy, coronal sections. Quantification was performed using ZEN 2011 software on 3 sections from each mouse (3 mice from each group, total n = 9). DG, dentate gyrus, LV, lateral ventricle, SVZ, subventricular zone, and cc, corpus callosum. Scale bar: 10 μm (magnification = ×63).

Mentions: In order to examine the effect of anti-EGF Ab treatment on the extent of oligodendrogenesis within the neuroproliferative niches, we compared BrdU+O4+ cells in the SVZ and the SGZ of the anti-EGF Ab- and IC-treated groups. Although we observed a slight trend towards increased numbers of BrdU+O4+ cells in the SGZ of anti-EGF Ab-treated EAE mice, this trend did not reach a level of significance (0.6 ± 0.1 in the anti-EGF Ab-treated group versus 0.4% ± 0.02 in the IC-treated group, P = NS, Figures 4(a), 4(b), and 4(c)). However, therapy with anti-EGF Ab led to a significant induction in %BrdU+O4+ cells within the SVZ (1.9 ± 0.1% in the anti-EGF Ab-treated group versus 0.4% ± 0.01 in the IC-treated group, P = 0.01, Figures 4(d), 4(e), and 4(f)).


Treatment with Anti-EGF Ab Ameliorates Experimental Autoimmune Encephalomyelitis via Induction of Neurogenesis and Oligodendrogenesis.

Amir-Levy Y, Mausner-Fainberg K, Karni A - Mult Scler Int (2014)

Increased numbers of de novo oligodendrocytes in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+O4+ cells in the SGZ and SVZ of IC-treated mice (a and d, resp.) and of anti-EGF Ab-treated mice (b and e, resp.) on day 18 after immunization. Quantification of %BrdU+O4+ cells in the SGZ and in the SVZ (c and f, correspondingly) revealed a nonsignificant trend for induction of BrdU+O4+ in the SGZ, along with a significant induction in BrdU+O4+ cells in the SVZ. Images were obtained using a confocal microscopy, coronal sections. Quantification was performed using ZEN 2011 software on 3 sections from each mouse (3 mice from each group, total n = 9). DG, dentate gyrus, LV, lateral ventricle, SVZ, subventricular zone, and cc, corpus callosum. Scale bar: 10 μm (magnification = ×63).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4295609&req=5

fig4: Increased numbers of de novo oligodendrocytes in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+O4+ cells in the SGZ and SVZ of IC-treated mice (a and d, resp.) and of anti-EGF Ab-treated mice (b and e, resp.) on day 18 after immunization. Quantification of %BrdU+O4+ cells in the SGZ and in the SVZ (c and f, correspondingly) revealed a nonsignificant trend for induction of BrdU+O4+ in the SGZ, along with a significant induction in BrdU+O4+ cells in the SVZ. Images were obtained using a confocal microscopy, coronal sections. Quantification was performed using ZEN 2011 software on 3 sections from each mouse (3 mice from each group, total n = 9). DG, dentate gyrus, LV, lateral ventricle, SVZ, subventricular zone, and cc, corpus callosum. Scale bar: 10 μm (magnification = ×63).
Mentions: In order to examine the effect of anti-EGF Ab treatment on the extent of oligodendrogenesis within the neuroproliferative niches, we compared BrdU+O4+ cells in the SVZ and the SGZ of the anti-EGF Ab- and IC-treated groups. Although we observed a slight trend towards increased numbers of BrdU+O4+ cells in the SGZ of anti-EGF Ab-treated EAE mice, this trend did not reach a level of significance (0.6 ± 0.1 in the anti-EGF Ab-treated group versus 0.4% ± 0.02 in the IC-treated group, P = NS, Figures 4(a), 4(b), and 4(c)). However, therapy with anti-EGF Ab led to a significant induction in %BrdU+O4+ cells within the SVZ (1.9 ± 0.1% in the anti-EGF Ab-treated group versus 0.4% ± 0.01 in the IC-treated group, P = 0.01, Figures 4(d), 4(e), and 4(f)).

Bottom Line: Methods.No immunosuppressive effect was found.Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.

View Article: PubMed Central - PubMed

Affiliation: Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv 64239, Israel.

ABSTRACT
Background. The neural stem cells (NSCs) migrate to the damaged sites in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). However, the differentiation into neurons or oligodendrocytes is blocked. Epidermal growth factor (EGF) stimulates NSC proliferation and mobilization to demyelinated lesions but also induces astrogenesis and glial scar. Objective. To examine the clinical and histopathological effects of EGF neutralization on EAE. Methods. EAE-induced SJL mice were intravenously treated with either anti-EGF neutralizing antibody (Ab) or isotype control or PBS. On day 9 after immunization, 3 mice of each group were daily treated for 9 days with BrdU and then sacrificed for immunohistochemical analysis. Results. Treatment with anti-EGF Ab significantly ameliorated EAE symptoms during the second relapse. Anti-EGF Ab induced a shift from BrdU(+)GFAP(+) NSCs to BrdU(+)DCX(+) neuroblasts in the subventricular zone (SVZ), increased BrdU(+)NeuN(+) neurons in the granular cell layer of the dentate gyrus, and increased BrdU(+)O4(+) oligodendrocytes in the SVZ. There was no change in the inflammatory infiltrates in response to anti-EGF Ab. Conclusions. Therapy with anti-EGF Ab ameliorates EAE via induction of neurogenesis and oligodendrogenesis. No immunosuppressive effect was found. Further investigation is needed to support these notions of beneficial effect of anti-EGF Ab in MS.

No MeSH data available.


Related in: MedlinePlus