beta-N-methylamino-L-alanine induced in vivo retinal cell death.
Controversial debates still remain around the nature of the etiologic agent responsible for Amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC) whose incidence is unusually high among the population of the pacific island of Guam. It has been hypothesized that the neurotoxin beta-N-methylamino-L-alanine (L-BMAA) produced by cyanobacteria in the roots of Cycas Circinalis seeds might trigger ALS/PDC. Frequently observed in patients with ALS/PDC, retinopathy is one of the clinical features of the disease. The effect of the L-BMAA on cell viability was examined in vivo by measuring the electrophysiological activity of the mouse retinal neurons by electroretinography recordings. Intra-ocular injections of L-BMAA selectively reduced the b-wave amplitude, without affecting neither the a-wave amplitude nor the a- and b-latencies. The cell death of retinal cells was evidenced by histology on retina sections, caspase 3 activation, incorporation of propidium iodide and production of reactive oxygen species. Co-injection with the specific NMDA antagonist, MK-801, significantly protected the retinal neurons from L-BMAA/NMDA-induced apoptosis. We provide evidence that L-BMAA induced neuronal cell death in vivo supporting a direct causal link between L-BMAA and neuronal damages.
Santucci
Serena
S
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Valbonne, France.
Zsürger
Nicole
N
Chabry
Joëlle
J
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D000087522:Cyanobacteria Toxins; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004585:Electrooculography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D013997:Time Factors
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017382:Reactive Oxygen Species; C001824:beta-N-methylamino-L-alanine; D011419:Propidium; D016291:Dizocilpine Maleate; D053148:Caspase 3