Protective effects of L-arginine on Alzheimer's disease: Modulating hippocampal nitric oxide levels and memory deficits in aluminum chloride-induced rat model.

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, ß-amyloid (ßA) 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 ßA (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), ß-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. ßA 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 ßA, AlCl3 (25 µg/rat) caused accumulation of ßA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and ß-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.

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. ßA (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.

Sonochemical synthesis, characterization, and effects of temperature, power ultrasound and reaction time on the morphological properties of two new nanostructured mercury(II) coordination supramolecule compounds.

Two new mercury(II) coordination supramolecular compounds (CSCs) (1D and 0D), [Hg(L)(I)2]n (1) and [Hg2(L')2(SCN)2]·2H2O (2) (L=2-amino-4-methylpyridine and L'=2,6-pyridinedicarboxlic acid), have been synthesized under different experimental conditions. Micrometric crystals (bulk) or nano-sized materials have been obtained depending on using the branch tube method or sonochemical irradiation. All materials have been characterized by field emission scanning electron microscope (FESEM), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and FT-IR spectroscopy. Single crystal X-ray analyses on compounds 1 and 2 show that Hg2+ ions are 4-coordinated and 5-coordinated, respectively. Topological analysis shows that the compound 1 and 2 have 2C1, sql net. The thermal stability of compounds 1 and 2 in bulk and nano-size has been studied by thermal gravimetric (TG), differential thermal analyses (DTA) for 1 and differential scanning calorimetry (DSC) for 2, respectively. Also, by changing counter ions were obtained various structures 1 and 2 (1D and 0D, respectively). The role of different parameters like power of ultrasound irradiation, reaction time and temperature on the growth and morphology of the nano-structures are studied. Results suggest that increasing power ultrasound irradiation and temperature together with reducing reaction time and concentration of initial reagents leads to a decrease in particle size.