Nitric oxide synthase inhibitors protect cholinergic neurons against AlCl3 excitotoxicity in the rat brain.
The present experiment was carried out to determine the effectiveness of nitric oxide synthase inhibitors: 7-nitroindazole and aminoguanidine in modulating the toxicity of aluminium chloride on acetylcholine esterase activity, as well as behavioural and morphological changes of Wistar rats. For biochemical analysis the animals were killed 10 min, 3 h, 3 days and 30 days after the treatment and forebrain cortex, striatum, basal forebrain and hippocampus were removed. The biochemical changes observed in neuronal tissues show that nitric oxide synthase inhibitors exert as protective action in aluminium chloride-treated animals. In the present study, active avoidance learning was significantly impaired after aluminium chloride injection, while pretreatment with nitric oxide synthase inhibitors prevented the behavioural deficits caused between 26th and 30th day after intrahippocampal application of neurotoxin. Our data suggest that aluminium may cause learning and memory deficits, while the treatment with specific nitric oxide synthase inhibitors may prevent learning and memory deficits caused by aluminium chloride. We have also applied immunohistochemical techniques to identify neuronal- and inducible-nitric oxide synthase expression 30 days after aluminium chloride and nitric oxide synthase inhibitors injections. Our data suggest that 7-nitroindazole and aminoguanidine can be effective in the protection of toxicity induced by aluminium chloride.
Stevanović
Ivana D
ID
Military Medical Academy, Institute for Medical Research, Belgrade, 11 000 Belgrade, Serbia. ivanav13@yahoo.ca
Jovanović
Marina D
MD
Colić
Miodrag
M
Jelenković
Ankica
A
Bokonjić
Dubravko
D
Ninković
Milica
M
D000110:Acetylcholinesterase / Q000378:metabolism*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002712:Chlorides / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D017607:Aluminum Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D018696:Neuroprotective Agents; D009498:Neurotoxins; D000077410:Aluminum Chloride; D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase; C004479:pimagedine; C080122:7-nitroindazole