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

• DOI: 10.1007/s11064-021-03460-5
• Publication Date: 2021-10-09T07:03:48Z
• Authors: Fernanda Cardoso ...; Bruna da Silveira...; Julia Eisenhardt ...; Juliane Cardoso; Luiza Spohr; Karina Pereira Lu...; Mayara Sandrielly...; Fabiano Barbosa C...; Jessie Martins Gu...; Anelize de Olivei...; Francieli Moro St...; Roselia Maria Spa...
• Keywords: Male; 0301 basic medicine; Memory Disorders; 0303 health sciences; Scopolamine; Cholinergic Agents; Ion Pumps; Inosine; Rats; 3. Good health; Oxidative Stress; 03 medical and health sciences; Acetylcholinesterase; Animals; Cognitive Dysfunction; Rats, Wistar; Maze Learning; Oxidation-Reduction; Memory Consolidation

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.