The effects of L-arginine on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide


1 Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


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 CA1area 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 andP < 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.


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