Beta-amyloid induced reduction in synaptic transmission is reversed by inhibitors of nitric oxide synthase.
beta-Amyloid has been shown to be neurotoxic in vivo and in vitro. Free radical production and subsequent lipid oxidation after beta-amyloid application have been observed in vitro and are considered to be factors that contribute to the neurotoxicity. Field recordings in the area CA1 for 3 weeks showed a dose-dependent effect on amplitude after intracerebroventricular (i.c.v.) injections of 1, 5 or 10 nmol beta-amyloid (25-35). The nitric oxide synthase inhibitors 7-nitro indazole (30 mg/kg, i.p.) and 1-(2-trifluoromethylphenyl)imidazole (150 nmol, i.c.v.) which preferentially inhibit the neuronal isoform prevented this beta-amyloid-induced decay of synaptic transmission. The protective effect of these inhibitors was reversed by L-arginine (200 mg/kg, i.p.). The results support the theory that nitric oxide production contributes to beta-amyloid-induced neuronal degeneration or reduction of neurotransmission.
Hölscher
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University College Dublin, Department of Physiology, Ireland.
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005609:Free Radicals; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011109:Polymethacrylic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D005609:Free Radicals; D007191:Indazoles; D011109:Polymethacrylic Acids; C091347:vinyl ethyl methacrylate; D001120:Arginine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole