Ergothioneine treatment protects neurons against N-methyl-D-aspartate excitotoxicity in an in vivo rat retinal model.
Injection of the glutamate agonist N-methyl-D-aspartate into the vitreous body of the rat eye resulted in a number of morphological changes in the retina. Most apparent was a dramatic reduction in the density and sizes of neurons accompanied by a decrease in amyloid precursor protein and glial fibrillary acidic protein immunoreactivity. Cell counts revealed that 81% of ganglion cells and 43% of non-ganglion cells were lost as a result of the treatment. However, in animals treated with the antioxidant ergothioneine, these figures dropped to 44 and 31%, respectively. Thus, ergothioneine appears to be neuroprotective in this system and the data suggest that antioxidants may provide a useful means of modulating glutamate-based toxicity.
Department of Neuroinflammation, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK.
Juliet A
JA
Moncaster
Desmond T
DT
Walsh
Stephen M
SM
Gentleman
Ling-Sun
LS
Jen
Okezie I
OI
Aruoma
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004880:Ergothioneine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D004880:Ergothioneine