Involvement of brain-derived neurotrophic factor in time-dependent neurodegeneration in the murine superior colliculus after intravitreal injection of N-methyl-D-aspartate.
OBJECTIVE
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.
1Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Hirotaka
H
Tanaka
Yasushi
Y
Ito
Shinsuke
S
Nakamura
Masamitsu
M
Shimazawa
Hideaki
H
Hara
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004333:Drug Administration Routes; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000008:administration & dosage* / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D013477:Superior Colliculi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D016202:N-Methylaspartate