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Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons.
Graefes Arch Clin Exp Ophthalmol. 2000 Mar; 238(3):243-8.GA

Abstract

BACKGROUND

Both in vivo and in vitro studies suggest that excess stimulation of non-NMDA receptors can result in massive neuronal death in the retina. In particular, murine amacrine neurons have been known to show marked susceptibility to the toxic effects of kainate.

PURPOSE

This study was designed to examine and characterize the role of N-methyl-D-aspartate (NMDA) receptor vs non-NMDA receptor in glutamate-induced neurotoxicity in the retina.

METHODS

Primary cultures obtained from fetal rat retina (gestation day 16-19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Electrophysiological studies using patch-clamp techniques were performed to record whole-cell currents evoked by these excitatory amino acids.

RESULTS

Removal of extracellular Ca2+ from the medium or application of MK-801 reduced the extent of cell death induced by the brief exposure to glutamate, NMDA, and kainate. By contrast, cell death induced by a 60-min exposure to kainate was not affected by MK-801. The electrophysiological study demonstrated that MK-801 abolished the whole-cell currents evoked by NMDA but had no effect on those induced by kainate or AMPA.

CONCLUSION

These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultured fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure.

Authors+Show Affiliations

Zhang S
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
Kashii S
No affiliation info available
Yasuyoshi H
No affiliation info available
Honda Y
No affiliation info available
Ujihara H
No affiliation info available
Sasa M
No affiliation info available
Tamura Y
No affiliation info available
Akaike A
No affiliation info available

MeSH

AnimalsCalciumCell DeathCell SurvivalCells, CulturedDizocilpine MaleateExcitatory Amino Acid AgonistsGlutamic AcidKainic AcidMembrane PotentialsN-MethylaspartateNeuronsNeuroprotective AgentsPatch-Clamp TechniquesRatsReceptors, N-Methyl-D-AspartateRetinaalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10796040

Citation

Zhang, S, et al. "Involvement of NMDA-receptor in Kainate-induced Neurotoxicity in Cultured Fetal Retinal Neurons." Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie, vol. 238, no. 3, 2000, pp. 243-8.
Zhang S, Kashii S, Yasuyoshi H, et al. Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons. Graefes Arch Clin Exp Ophthalmol. 2000;238(3):243-8.
Zhang, S., Kashii, S., Yasuyoshi, H., Honda, Y., Ujihara, H., Sasa, M., Tamura, Y., & Akaike, A. (2000). Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie, 238(3), 243-8.
Zhang S, et al. Involvement of NMDA-receptor in Kainate-induced Neurotoxicity in Cultured Fetal Retinal Neurons. Graefes Arch Clin Exp Ophthalmol. 2000;238(3):243-8. PubMed PMID: 10796040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons. AU - Zhang,S, AU - Kashii,S, AU - Yasuyoshi,H, AU - Honda,Y, AU - Ujihara,H, AU - Sasa,M, AU - Tamura,Y, AU - Akaike,A, PY - 2000/5/5/pubmed PY - 2000/6/10/medline PY - 2000/5/5/entrez SP - 243 EP - 8 JF - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JO - Graefes Arch Clin Exp Ophthalmol VL - 238 IS - 3 N2 - BACKGROUND: Both in vivo and in vitro studies suggest that excess stimulation of non-NMDA receptors can result in massive neuronal death in the retina. In particular, murine amacrine neurons have been known to show marked susceptibility to the toxic effects of kainate. PURPOSE: This study was designed to examine and characterize the role of N-methyl-D-aspartate (NMDA) receptor vs non-NMDA receptor in glutamate-induced neurotoxicity in the retina. METHODS: Primary cultures obtained from fetal rat retina (gestation day 16-19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Electrophysiological studies using patch-clamp techniques were performed to record whole-cell currents evoked by these excitatory amino acids. RESULTS: Removal of extracellular Ca2+ from the medium or application of MK-801 reduced the extent of cell death induced by the brief exposure to glutamate, NMDA, and kainate. By contrast, cell death induced by a 60-min exposure to kainate was not affected by MK-801. The electrophysiological study demonstrated that MK-801 abolished the whole-cell currents evoked by NMDA but had no effect on those induced by kainate or AMPA. CONCLUSION: These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultured fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure. SN - 0721-832X UR - https://www.unboundmedicine.com/medline/citation/10796040/Involvement_of_NMDA_receptor_in_kainate_induced_neurotoxicity_in_cultured_fetal_retinal_neurons_ L2 - https://dx.doi.org/10.1007/s004170050351 DB - PRIME DP - Unbound Medicine ER -