Effects of Nitric Oxide (NO) Modulators on Cognitive Function and Brain Oxidative Stress in Experimental Model of Alzheimer’s Disease in Rats

In present study, we investigated the effects of NO modulators (L-arginine and L-NAME) in intracerebroventricular-streptozotocin (ICV-STZ, 3 mg/kg) induced rat model of sporadic AD (sAD). Pre-treatment with L-arginine (100 mg/kg/ip/day) improved ICV-STZ induced cognitive deficit in the Morris water maze (MWM) test when compared to the control (saline) group. Both memory acquisition (escape latency) and retention (probe trial) were affected by icv-STZ which were reversed after L-arginine treatment. The NO synthase inhibitor, L-NAME (10 mg/kg), on the other hand, did not have much influence on these parameters. In the fear based memory model (Passive Avoidance test, PA), ICV-STZ treated rats showed decreased latency period for entry into the dark chamber, which was reversed after L-arginine pre-treatment. In brain homogenates, there were decreased levels of reduced glutathione (GSH) and increased levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hippocampus, cortex and amygdala after ICV-STZ injection. Pre-treatment with L-arginine, restored GSH levels in hippocampus and 8OHdG level in cortex, towards baseline levels. These results provide experimental evidence for the attenuating effects of L-arginine on ICV-STZ induced cognitive dysfunctions which were associated with reduced oxidative stress in this model of sporadic Alzheimer`s Disease (sAD). It is inferred that NO and its interactions with reactive oxygen species could reduce age related cognitive deficits and that L-arginine could be a potential therapeutic supplement in the treatment of sAD.