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

Elevated numbers of de novo mature neurons in the GCL of anti-EGF Ab-treated EAE mice. Immunohistochemical labeling of BrdU+NeuN+ cells in the GCL of IC-treated mice (a) and of anti-EGF Ab-treated mice (b) on day 18 after immunization. Quantification of %BrdU+NeuN+ cells (c) revealed increased numbers of BrdU+NeuN+ in the GCL 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). GCL, granular cell layer. Scale bar: 10 μm (magnification = ×63).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4295609&req=5

fig3: Elevated numbers of de novo mature neurons in the GCL of anti-EGF Ab-treated EAE mice. Immunohistochemical labeling of BrdU+NeuN+ cells in the GCL of IC-treated mice (a) and of anti-EGF Ab-treated mice (b) on day 18 after immunization. Quantification of %BrdU+NeuN+ cells (c) revealed increased numbers of BrdU+NeuN+ in the GCL 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). GCL, granular cell layer. Scale bar: 10 μm (magnification = ×63).

Mentions: We next examined the effect of anti-EGF Ab treatment on the number of BrdU+NeuN+ mature neurons in the neuroproliferative niches. We detected a significant increase in the percentage of newborn cells expressing a neuronal nuclear (NeuN) marker, that is, %BrdU+NeuN+ cells, in the GCL of the dentate gyrus in response to treatment with anti-EGF Ab (0.5 ± 0.06% in anti-EGF group versus 0.2% ± 0.01 in the IC group, P = 0.02, Figures 3(a), 3(b), and 3(c)), suggesting that an EGF signaling blockade induced neuroblast differentiation into mature neurons within the GCL of the dentate gyrus at this time point of intervention.


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)

Elevated numbers of de novo mature neurons in the GCL of anti-EGF Ab-treated EAE mice. Immunohistochemical labeling of BrdU+NeuN+ cells in the GCL of IC-treated mice (a) and of anti-EGF Ab-treated mice (b) on day 18 after immunization. Quantification of %BrdU+NeuN+ cells (c) revealed increased numbers of BrdU+NeuN+ in the GCL 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). GCL, granular cell layer. Scale bar: 10 μm (magnification = ×63).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Elevated numbers of de novo mature neurons in the GCL of anti-EGF Ab-treated EAE mice. Immunohistochemical labeling of BrdU+NeuN+ cells in the GCL of IC-treated mice (a) and of anti-EGF Ab-treated mice (b) on day 18 after immunization. Quantification of %BrdU+NeuN+ cells (c) revealed increased numbers of BrdU+NeuN+ in the GCL 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). GCL, granular cell layer. Scale bar: 10 μm (magnification = ×63).
Mentions: We next examined the effect of anti-EGF Ab treatment on the number of BrdU+NeuN+ mature neurons in the neuroproliferative niches. We detected a significant increase in the percentage of newborn cells expressing a neuronal nuclear (NeuN) marker, that is, %BrdU+NeuN+ cells, in the GCL of the dentate gyrus in response to treatment with anti-EGF Ab (0.5 ± 0.06% in anti-EGF group versus 0.2% ± 0.01 in the IC group, P = 0.02, Figures 3(a), 3(b), and 3(c)), suggesting that an EGF signaling blockade induced neuroblast differentiation into mature neurons within the GCL of the dentate gyrus at this time point of intervention.

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