Abstract
There is evidence that high daily intake of aluminum (Al) is associated with an increased risk of dementia or cognitive decline. We injected L-arginine into the dorsal hippocampus (DH) of an AlCl3-induced Alzheimer's model and studied memory deficit, β-amyloid (βA) accumulation, neurodegeneration, and molecular changes. Male Wistar rats were cannulated unilaterally in the DH under a stereotaxic apparatus and a dose of AlCl3 (1-200 μg/rat) was injected into the CA1. After recovery, L-arginine and L-NAME (0.05-25 μg/rat) were injected into CA1 and animals were tested in novelty seeking task. One group received βA (2 μg/rat, intra CA1) as a reference group. Control groups received saline (1 μL/rat, intra-CA1) and galantamine (25 μg/rat, intra-CA1), respectively. Finally, rats were anesthetized and hippocampal tissues were isolated on ice. Levels of neuronal NO synthase (nNOS), β-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. βA formation and the number of CA1 neurons were assessed by Congo red and Nissl staining. NOS activation by NADPH-diaphorase (NADPH-d) was investigated. All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. Like βA, AlCl3 (25 μg/rat) caused accumulation of βA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and β-secretase, but not sGC, showed a change consistent with Alzheimer's. However, prophylactic intervention of L-arginine at 3-9 μg/rat was protective, probably by nNOS stimulation in DH, as shown by NADPH-d assay. L-arginine may protect against Alzheimer's by increasing hippocampal NO levels.
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