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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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NeuN immunostaining of sections of the SC. A: Representative microphotographs of the superior colliculus (SC) are shown for the control group (untreated) for 180 days after N-methyl-D-aspartate (NMDA) injection (the contralateral side and the ipsilateral side). The scale bars represent 30 µm. B: The average number of neuronal nuclear specific protein (NeuN)-labeled neurons was counted in the SC. Each value represents the mean±SEM (n=4–11). The asterisk indicates p<0.05, while the double asterisk represents p<0.01 versus control (untreated mice; Dunnett’s test).
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f2: NeuN immunostaining of sections of the SC. A: Representative microphotographs of the superior colliculus (SC) are shown for the control group (untreated) for 180 days after N-methyl-D-aspartate (NMDA) injection (the contralateral side and the ipsilateral side). The scale bars represent 30 µm. B: The average number of neuronal nuclear specific protein (NeuN)-labeled neurons was counted in the SC. Each value represents the mean±SEM (n=4–11). The asterisk indicates p<0.05, while the double asterisk represents p<0.01 versus control (untreated mice; Dunnett’s test).

Mentions: NeuN, an antibody known as a neuron-specific antigen, selectively and clearly stains neuronal perikarya and nuclei [25]. NeuN and Nissl staining produce highly correlated estimates of neuronal density, size, and shape [26]. Furthermore, NeuN may be particularly useful when it is important to distinguish small neurons from glial cells. In our control mice, NeuN-positivity was seen in almost all neurons within the superficial layer of the SC (Figure 2A). In the NMDA-treated group, NeuN-labeled neurons were first seen to be significantly decreased in number in the contralateral SC at 90 days after NMDA injection; the number decreased to 69.2% (90 days) and 68.1% (180 days) of control after NMDA injection (Figure 2B). In contrast, no significant decrease in the number of NeuN-labeled neurons (versus control) was observed in the superficial layer of the ipsilateral SC at 3, 7, 30, 90, and 180 days (Figure 2B). Furthermore, no morphological differences in the SC were observed among the control and sham-treated mice (data not shown).


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)

NeuN immunostaining of sections of the SC. A: Representative microphotographs of the superior colliculus (SC) are shown for the control group (untreated) for 180 days after N-methyl-D-aspartate (NMDA) injection (the contralateral side and the ipsilateral side). The scale bars represent 30 µm. B: The average number of neuronal nuclear specific protein (NeuN)-labeled neurons was counted in the SC. Each value represents the mean±SEM (n=4–11). The asterisk indicates p<0.05, while the double asterisk represents p<0.01 versus control (untreated mice; Dunnett’s test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: NeuN immunostaining of sections of the SC. A: Representative microphotographs of the superior colliculus (SC) are shown for the control group (untreated) for 180 days after N-methyl-D-aspartate (NMDA) injection (the contralateral side and the ipsilateral side). The scale bars represent 30 µm. B: The average number of neuronal nuclear specific protein (NeuN)-labeled neurons was counted in the SC. Each value represents the mean±SEM (n=4–11). The asterisk indicates p<0.05, while the double asterisk represents p<0.01 versus control (untreated mice; Dunnett’s test).
Mentions: NeuN, an antibody known as a neuron-specific antigen, selectively and clearly stains neuronal perikarya and nuclei [25]. NeuN and Nissl staining produce highly correlated estimates of neuronal density, size, and shape [26]. Furthermore, NeuN may be particularly useful when it is important to distinguish small neurons from glial cells. In our control mice, NeuN-positivity was seen in almost all neurons within the superficial layer of the SC (Figure 2A). In the NMDA-treated group, NeuN-labeled neurons were first seen to be significantly decreased in number in the contralateral SC at 90 days after NMDA injection; the number decreased to 69.2% (90 days) and 68.1% (180 days) of control after NMDA injection (Figure 2B). In contrast, no significant decrease in the number of NeuN-labeled neurons (versus control) was observed in the superficial layer of the ipsilateral SC at 3, 7, 30, 90, and 180 days (Figure 2B). Furthermore, no morphological differences in the SC were observed among the control and sham-treated mice (data not shown).

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