Protective Effect of L-Arginine in an Animal Model of Alzheimer's Disease Induced by Intra-Hippocampal Injection of AlCl3.

Background And Objective: Aluminum chloride (AlCl3) can impair spatial memory recovery. We investigated the protective effect of L-arginine, a precursor of nitric oxide (NO), on memory retrieval in an Alzheimer's animal model induced by AlCl3 at intra-hippocampal CA1 using a seeking behavior practice.

Materials And Methods: Wistar rats were deeply anesthetized and cannulated at CA1 (AP: -3.8 mm, L: ±2.2 mm, V: 3 mm), and received once AlCl3 (1-200 μg/rat, intra-CA1), on day of cannulation under stereotaxic device. After a week of recovery, they experienced the novelty task with a three-stage paradigm and injected L-arginine (0.05-25 μg/rat) intra-CA1, pretesting. L-NAME, the neuronal NO synthase inhibitor was administered before L-arginine effective doses in the test stage. Also, a reference group exclusively received beta-amyloid 2 μg/rat. Control group solely received saline. Finally, after euthanasia of rat, the hippocampal sample was collected on ice and evaluated by immunohistochemical marking and specific staining.

Results: AlCl3 caused novelty-seeking behavior without meaningful change in animal locomotor activity. βA (2 μg/rat, intra-CA1) affected the rat's grooming, causing it to stop further in the new side. Pretest injection of L-arginine restored behavior in AlCl3-treated rats; however, this effect was stopped by L-NAME pretreatment, indicating NO involvement. CA1 did not show necrotic change due to AlCl3 exposure; however, neurofibrillary tangles were accumulated in the region.

Conclusions: Prophylaxis with L-arginine probably due to NO has a protective role against the dangerous effect of AlCl3 on the function of neurons in the cortical hippocampus.