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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

Reduced numbers of NSCs and increased numbers of neuroblasts in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+GFAP+ cells and BrdU+DCX+ cells in the 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+GFAP+ cells (c) and of %BrdU+DCX+ cells (f) revealed reduced numbers of BrdU+GFAP+ cells and increased numbers of BrdU+DCX+ cells in the SVZ of anti-EGF Ab-treated EAE mice compared to IC-treated mice. 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). LV, lateral ventricle, SVZ, subventricular zone. Scale bar: 100 μm.
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fig2: Reduced numbers of NSCs and increased numbers of neuroblasts in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+GFAP+ cells and BrdU+DCX+ cells in the 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+GFAP+ cells (c) and of %BrdU+DCX+ cells (f) revealed reduced numbers of BrdU+GFAP+ cells and increased numbers of BrdU+DCX+ cells in the SVZ of anti-EGF Ab-treated EAE mice compared to IC-treated mice. 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). LV, lateral ventricle, SVZ, subventricular zone. Scale bar: 100 μm.

Mentions: As demonstrated in Figures 2(a), 2(b), and 2(c), the percentage of BrdU+GFAP+ NSCs in the SVZ were lower in the anti-EGF Ab-treated group compared to the IC-treated group (1.1% ± 0.1 versus 2.4% ± 0.2, P = 0.04, resp.). We also detected a substantial elevation in the percentage of proliferating neuroblasts expressing doublecortin (%BrdU+DCX+) in the SVZ in response to EGF blockade (16.1 ± 0.1% in the anti-EGF group versus 2.2 ± 0.7% in the IC group, P = 0.006, Figures 2(d), 2(e), and 2(f)), suggesting that the EGF blockade promoted the differentiation of SVZ NSCs to DCX+ neuroblasts. Interestingly, we did not detect any group differences in the numbers of BrdU+GFAP+ or of BrdU+DCX+ in the hippocampus subgranular zone (SGZ) of the dentate gyrus (data not shown).


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)

Reduced numbers of NSCs and increased numbers of neuroblasts in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+GFAP+ cells and BrdU+DCX+ cells in the 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+GFAP+ cells (c) and of %BrdU+DCX+ cells (f) revealed reduced numbers of BrdU+GFAP+ cells and increased numbers of BrdU+DCX+ cells in the SVZ of anti-EGF Ab-treated EAE mice compared to IC-treated mice. 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). LV, lateral ventricle, SVZ, subventricular zone. Scale bar: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4295609&req=5

fig2: Reduced numbers of NSCs and increased numbers of neuroblasts in the SVZ in response to therapy with anti-EGF Ab. Immunohistochemical labeling of BrdU+GFAP+ cells and BrdU+DCX+ cells in the 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+GFAP+ cells (c) and of %BrdU+DCX+ cells (f) revealed reduced numbers of BrdU+GFAP+ cells and increased numbers of BrdU+DCX+ cells in the SVZ of anti-EGF Ab-treated EAE mice compared to IC-treated mice. 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). LV, lateral ventricle, SVZ, subventricular zone. Scale bar: 100 μm.
Mentions: As demonstrated in Figures 2(a), 2(b), and 2(c), the percentage of BrdU+GFAP+ NSCs in the SVZ were lower in the anti-EGF Ab-treated group compared to the IC-treated group (1.1% ± 0.1 versus 2.4% ± 0.2, P = 0.04, resp.). We also detected a substantial elevation in the percentage of proliferating neuroblasts expressing doublecortin (%BrdU+DCX+) in the SVZ in response to EGF blockade (16.1 ± 0.1% in the anti-EGF group versus 2.2 ± 0.7% in the IC group, P = 0.006, Figures 2(d), 2(e), and 2(f)), suggesting that the EGF blockade promoted the differentiation of SVZ NSCs to DCX+ neuroblasts. Interestingly, we did not detect any group differences in the numbers of BrdU+GFAP+ or of BrdU+DCX+ in the hippocampus subgranular zone (SGZ) of the dentate gyrus (data not shown).

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