Protective Effects of Inosine on Memory Consolidation in a Rat Model of Scopolamine-Induced Cognitive Impairment: Involvement of Cholinergic Signaling, Redox Status, and Ion Pump Activities.

This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.

Los poros y los canales iónicos regulan la actividad celular / The pores and the ionics canals regulate the cellular activity

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Arsenate reductases in prokaryotes and eukaryotes.

The ubiquity of arsenic in the environment has led to the evolution of enzymes for arsenic detoxification. An initial step in arsenic metabolism is the enzymatic reduction of arsenate [As(V)] to arsenite [As(III)]. At least three families of arsenate reductase enzymes have arisen, apparently by convergent evolution. The properties of two of these are described here. The first is the prokaryotic ArsC arsenate reductase of Escherichia coli. The second, Acr2p of Saccharomyces cerevisiae, is the only identified eukaryotic arsenate reductase. Although unrelated to each other, both enzymes receive their reducing equivalents from glutaredoxin and reduced glutathione. The structure of the bacterial ArsC has been solved at 1.65 A. As predicted from its biochemical properties, ArsC structures with covalent enzyme-arsenic intermediates that include either As(V) or As(III) were observed. The yeast Acr2p has an active site motif HC(X)(5)R that is conserved in protein phosphotyrosine phosphatases and rhodanases, suggesting that these three groups of enzymes may have evolved from an ancestral oxyanion-binding protein.

Na+ and K+ dependence of morphological changes of cultured rat cortical astrocytes.

Cultured astrocytes display flattened, polygonal morphology in the absence of stimuli, and change into process-bearing stellate cells in response to specific stimuli. In the present study, we investigated possible role of Na+, K+ and Ca2+ in this morphological change of cultured rat cortical astrocytes. Astrocyte stellation induced by dibutyryl cyclic AMP (1 mM), phorbol ester (100 nM) or amyloid beta peptide (20 microM) was partly suppressed by replacing NaCl with choline chloride or LiCl in the extracellular medium or by adding KCl, and was completely abolished by replacing NaCl with KCl. Furthermore, the astrocyte stellation was blocked by the specific Na+-K+ pump inhibitor ouabain. However, it was not significantly affected by removing CaCl2 from the extracellular medium nor by adding the voltage-dependent Ca2+ channel blocker nicardipine. These results suggest that Na+ and K+, but not Ca2+, electrochemical gradients across the plasma membrane are necessary for morphological changes of astrocytes. In addition, amyloid beta25-35-induced stellation was most susceptible to changing Na+ and K+ concentrations or ouabain, while phorbol ester-induced stellation was least sensitive, demonstrating that the Na+ and K+ dependence differs among stimuli.