ABSTRACT
BACKGROUND: The role of neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced memory and synaptic plasticity impairment was investigated. METHODS: The rats were divided and treated as follows: (1) control (saline), (2) LPS, (3) 7NI (7-nitroindazole as a nNOS inhibitor)-LPS and (4) 7NI. RESULTS: In a Morris water maze, the LPS group took a longer amount of time and traveled a greater distance to reach the platform, this was prevented by 7NI. Malondialdehyde (MDA) and nitric oxide (NO) metabolites in the hippocampus of the LPS group were higher while the total thiol, superoxide dismutase and catalase were lower than that of the controlled specimen. Pre-treatment using 7NI prevented the changes in the biochemical criteria. The slope and amplitude of the field excitatory post-synaptic potential (fEPSP) in the LPS group decreased, whereas in 7NI-LPS group they increased. CONCLUSION: It is suggested that inhibition of nNOS by 7NI improves the deleterious effects of LPS by reducing NO metabolites and the brain tissues oxidative damage.
Subject(s)
Lipopolysaccharides/pharmacokinetics , Neuronal Plasticity/drug effects , Nitric Oxide Synthase Type I/metabolism , Spatial Memory/drug effects , Animals , Enzyme Inhibitors/pharmacology , Hippocampus/drug effects , Hippocampus/metabolism , Indazoles/pharmacology , Malondialdehyde/metabolism , Maze Learning/drug effects , Nitric Oxide/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: An important role of nitric oxide (NO) in neuroinflammation has been suggested. It is also suggested that NO has a critical role in learning and memory. Neuro-inflammation induced by lipopolysaccharide (LPS) has been reported that deteriorates learning and memory. The effect of L-arginine (LA) as a precursor of NO on LPS-induced spatial learning and memory and neuronal plasticity impairment was evaluated. MATERIALS AND METHODS: The animals were grouped into: (1) Control, (2) LPS, (3) LA-LPS, and (4) LA. The rats received intraperitoneally LPS (1 mg/kg) 2 h before experiments and LA (200 mg/kg) 30 min before LPS. The animals were examined in Morris water maze (MWM). Long-term potentiation (LTP) from CA1 area of the hippocampus was also assessed by 100 Hz stimulation in the ipsilateral Schaffer collateral pathway. RESULTS: In MWM, time latency and traveled path were higher in LPS group than the control group (P < 0.001) whereas in LA-LPS group they were shorter than LPS group (P < 0.001). The amplitude and slope of field excitatory postsynaptic potential (fEPSP) decreased in LPS group compared to control group (P < 0.05 and P < 0.01) whereas, there was not any significant difference in these parameters between LPS and LA-LPS groups. CONCLUSION: Administration of LPS impaired spatial memory and synaptic plasticity. Although LA ameliorated deleterious effects of LPS on learning of spatial tasks, it could not restore LPS-induced LTP impairment.
