Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

Stress affects multiple organs in the body in addition to the brain including the liver. We aimed to assess the effects of blocking N-methyl-D-aspartate (NMDA) glutamate receptors by memantine on the liver in acute and repeated restraint stress. Forty two male albino rats divided into seven groups; control, Acute restraint stress (ARS), ARS+memantine, repeated restraint stress, repeated restraint +memantine and positive control groups. We measured serum iron, zinc, alanine transferase and Aspartame transferase, hepatic malondialdehyde, tumor necrosis factor-alpha (TNF-α), glutathione peroxidase, Superoxide dismutase, metallothionein content, zinc transporter ZRT/IRT-like Protein 14 mRNA expression, hepcidin expression. We had a histopathological evaluation by histological staining and immunostaining for glial fibrillary acidic protein and synaptophysin expression as markers of hepatic stellate cells (HSCs) activation. Both ARS and repeated stress increased markers of hepatic cell injury, oxidative stress, and HSCs activation. Blocking NMDA by Memantine offered hepatoprotective effect in acute and repeated restraint stress and decreased hepatic cell injury, oxidative stress, and HSCs activation. KEYWORDS:Acute stress repeated stress, Restraint, liver, memantine In the current study, we explored the effects of acute and repeated restraint stress on the liver and the impact of blocking NMDA receptors by the memantine (the uncompetitive NMDA receptor antagonist) on the markers of hepatocellular injury, oxidative stress, and hepatic stellate cells (HSCs) activation. -METHODS: I-Experimental Animals:The experimental procedures, animal handling, sampling, and scarification were done according to the Guide for the care and use of laboratory animals, Eighth Edition (2011) B) Determination of liver functionsSerum ALT and AST were determined enzymatically using commercially available kits (Bioclin, Santa Coloma, Spain). C) Measurement of MDATissue MDA was determined using the thiobarbituric acid reactive substance assay, according to Wills (1987).Briefly; a tissue specimen of 0.1 g was homogenized in 0.15 mol KCl at a ratio of 1-9 ml with a glass homogeniser. One volume of homogenate was mixed with two volumes of a stock solution of 20% w/v trichloroacetic acid, 0.375% w/v thiobarbituric acid and 0.25 mol hydrochloric acid. The solution was heated for 15 min in a boiling water bath. After cooling, the precipitate was removed by centrifugation at 1000 g for 10 min.The absorbance of the clear supernatant was determined at 535 nm and MDA concentration calculated using the standard curve. The cDNA was synthesized from 1 µg RNA using SuperScript III First-Strand Synthesis System as described in the manufacturer's protocol (Invitrogen, Life Technologies). In brief, one µg of total RNA mixed with 50 µM oligo (dT)20, 50 ng/µL random primers, and ten mM dNTP mix in a total volume of 10 µL. The mixture incubated at 56 °C for 5 min, then placed on ice for 3 min. The reverse transcriptase master mix containing 2 µL of 10× RT buffer, ...