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Involvement of brain-derived neurotrophic factor in time-dependent neurodegeneration in the murine superior colliculus after intravitreal injection of N-methyl-D-aspartate.

Tanaka H, Ito Y, Nakamura S, Shimazawa M, Hara H - Mol. Vis. (2009)

Bottom Line: The number of neuronal nuclear specific protein (NeuN)-immunostained neurons showed a significant decrease in the contralateral SC at both 90 and 180 days after intravitreal NMDA injection.In contrast, the ipsilateral SC displayed no significant change in the number of NeuN-positive cells.Hence, these findings may provide useful information concerning the pathological mechanisms of several disorders accompanied by retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.

ABSTRACT

Purpose: To clarify the effects on the visual pathway that occur following retinal damage, we examined the morphological alterations present in the superior colliculus (SC) after N-methyl-D-aspartate (NMDA)-induced retinal damage in mice.

Methods: NMDA was injected into the vitreous body of the left eye in mice to induce retinal damage. The time-dependent neuronal degeneration in the SC was assessed using immunohistochemistry.

Results: The number of neuronal nuclear specific protein (NeuN)-immunostained neurons showed a significant decrease in the contralateral SC at both 90 and 180 days after intravitreal NMDA injection. In contrast, the ipsilateral SC displayed no significant change in the number of NeuN-positive cells. An increase in glial fibrillary acid protein (GFAP) immunoreactivity was observed in the contralateral SC at 7, 30, and 90 days after NMDA injection and in the ipsilateral SC at 7 days, while brain-derived neurotrophic factor (BDNF) expression was increased in the contralateral SC at 30 and 90 days. In the contralateral SC, some GFAP-positive astroglial cells also exhibited BDNF at 30 days after NMDA injection.

Conclusions: Evidence of time-dependent morphological neuronal degeneration along the retinocollicular pathway from the retina to the SC was detected at 90 and 180 days, but not at 30 days, after NMDA-induced retinal damage. This neurodegeneration was preceded by an increase in BDNF expression in the SC, specifically at 30 and 90 days after NMDA injection. Hence, these findings may provide useful information concerning the pathological mechanisms of several disorders accompanied by retinal degeneration.

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Colocalization of BDNF with GFAP by double immunofluorescence. A: Schematic drawing shows the coronal section through the level of the superior colliculus (SC; bregma −3.40 mm) in mice. The boxed area is the region of the superficial layer in the contralateral SC. Representative photographs show brain-derived neurotrophic factor (BDNF; B and C) and glial fibrillary acid protein (GFAP; D and E) immunostaining, and BDNF/GFAP (F and G) double-immunostaining of the contralateral SC at 30 days after intravitreal N-methyl-D-aspartate (NMDA) injection in mice. Some BDNF-expressing cells (B and C, green) were colocalized with GFAP-positive astroglial cells (D and E, red), as indicated by the yellow color in F (merge of B and D) and G (merge of C and E). The scale bars represents 50 µm (B, D, and F) or 10 µm (C, E, and G).
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f5: Colocalization of BDNF with GFAP by double immunofluorescence. A: Schematic drawing shows the coronal section through the level of the superior colliculus (SC; bregma −3.40 mm) in mice. The boxed area is the region of the superficial layer in the contralateral SC. Representative photographs show brain-derived neurotrophic factor (BDNF; B and C) and glial fibrillary acid protein (GFAP; D and E) immunostaining, and BDNF/GFAP (F and G) double-immunostaining of the contralateral SC at 30 days after intravitreal N-methyl-D-aspartate (NMDA) injection in mice. Some BDNF-expressing cells (B and C, green) were colocalized with GFAP-positive astroglial cells (D and E, red), as indicated by the yellow color in F (merge of B and D) and G (merge of C and E). The scale bars represents 50 µm (B, D, and F) or 10 µm (C, E, and G).

Mentions: To identify other cells that were positive for BDNF, we performed double immunofluorescence for BDNF and GFAP in brain sections containing the SC after the intravitreal NMDA injection. Some GFAP-positive astroglial cells exhibited BDNF in the superficial layer of the contralateral SC at 30 days after NMDA injection (Figure 5).


Involvement of brain-derived neurotrophic factor in time-dependent neurodegeneration in the murine superior colliculus after intravitreal injection of N-methyl-D-aspartate.

Tanaka H, Ito Y, Nakamura S, Shimazawa M, Hara H - Mol. Vis. (2009)

Colocalization of BDNF with GFAP by double immunofluorescence. A: Schematic drawing shows the coronal section through the level of the superior colliculus (SC; bregma −3.40 mm) in mice. The boxed area is the region of the superficial layer in the contralateral SC. Representative photographs show brain-derived neurotrophic factor (BDNF; B and C) and glial fibrillary acid protein (GFAP; D and E) immunostaining, and BDNF/GFAP (F and G) double-immunostaining of the contralateral SC at 30 days after intravitreal N-methyl-D-aspartate (NMDA) injection in mice. Some BDNF-expressing cells (B and C, green) were colocalized with GFAP-positive astroglial cells (D and E, red), as indicated by the yellow color in F (merge of B and D) and G (merge of C and E). The scale bars represents 50 µm (B, D, and F) or 10 µm (C, E, and G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2664844&req=5

f5: Colocalization of BDNF with GFAP by double immunofluorescence. A: Schematic drawing shows the coronal section through the level of the superior colliculus (SC; bregma −3.40 mm) in mice. The boxed area is the region of the superficial layer in the contralateral SC. Representative photographs show brain-derived neurotrophic factor (BDNF; B and C) and glial fibrillary acid protein (GFAP; D and E) immunostaining, and BDNF/GFAP (F and G) double-immunostaining of the contralateral SC at 30 days after intravitreal N-methyl-D-aspartate (NMDA) injection in mice. Some BDNF-expressing cells (B and C, green) were colocalized with GFAP-positive astroglial cells (D and E, red), as indicated by the yellow color in F (merge of B and D) and G (merge of C and E). The scale bars represents 50 µm (B, D, and F) or 10 µm (C, E, and G).
Mentions: To identify other cells that were positive for BDNF, we performed double immunofluorescence for BDNF and GFAP in brain sections containing the SC after the intravitreal NMDA injection. Some GFAP-positive astroglial cells exhibited BDNF in the superficial layer of the contralateral SC at 30 days after NMDA injection (Figure 5).

Bottom Line: The number of neuronal nuclear specific protein (NeuN)-immunostained neurons showed a significant decrease in the contralateral SC at both 90 and 180 days after intravitreal NMDA injection.In contrast, the ipsilateral SC displayed no significant change in the number of NeuN-positive cells.Hence, these findings may provide useful information concerning the pathological mechanisms of several disorders accompanied by retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: 1Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.

ABSTRACT

Purpose: To clarify the effects on the visual pathway that occur following retinal damage, we examined the morphological alterations present in the superior colliculus (SC) after N-methyl-D-aspartate (NMDA)-induced retinal damage in mice.

Methods: NMDA was injected into the vitreous body of the left eye in mice to induce retinal damage. The time-dependent neuronal degeneration in the SC was assessed using immunohistochemistry.

Results: The number of neuronal nuclear specific protein (NeuN)-immunostained neurons showed a significant decrease in the contralateral SC at both 90 and 180 days after intravitreal NMDA injection. In contrast, the ipsilateral SC displayed no significant change in the number of NeuN-positive cells. An increase in glial fibrillary acid protein (GFAP) immunoreactivity was observed in the contralateral SC at 7, 30, and 90 days after NMDA injection and in the ipsilateral SC at 7 days, while brain-derived neurotrophic factor (BDNF) expression was increased in the contralateral SC at 30 and 90 days. In the contralateral SC, some GFAP-positive astroglial cells also exhibited BDNF at 30 days after NMDA injection.

Conclusions: Evidence of time-dependent morphological neuronal degeneration along the retinocollicular pathway from the retina to the SC was detected at 90 and 180 days, but not at 30 days, after NMDA-induced retinal damage. This neurodegeneration was preceded by an increase in BDNF expression in the SC, specifically at 30 and 90 days after NMDA injection. Hence, these findings may provide useful information concerning the pathological mechanisms of several disorders accompanied by retinal degeneration.

Show MeSH
Related in: MedlinePlus