Possible role of Sirtuin in neuronal mitochondrial energy cascade for memory cognition

Abstract

Background Sirtuin (SIRT4) binds to adenine nucleotide translocator (ANT), which transports ATP into the cytosol and ADP into the mitochondrial matrix, thereby providing a substrate for ATP synthase. Objective To investigate the role of Sirtuin in mitochondrial energy deprivation in 3-NP induced neurodegeneration model in rats. Material and methods Adult Wistar albino rats (180-220 g) were clustered in 5 different groups, each comprising 6 animals (n=6). Saline treatment was given to the animals of normal group. 3-NP (10 mg/kg i.p.) was administered to the animals of different test groups for 14 days to induce neurodegeneration. Test drugs like Resveratrol, a Sirtuin activator (10 mg/kg, i.p.), Lithium chloride, a GSK inhibitor (10 mg/kg, i.p.) and Haloperidol, a GSK activator (1 mg/kg, i.p.) were given from 1st to 14th day to the animals. Behavioral assessments were performed from 21st day to 30th day. Results Administration of 3-NP caused significant loss in contextual learning and memory (on Morris water maze); memory related motor coordination (on balance beam test); and loss of exploratory behavior (in open field test). Treatment with Resveratrol and lithium chloride in individual group produced significant restoration of memory dysfunctions, and the effect caused by resveratrol was inhibited due to haloperidol given concomitantly. Similarly, the level of oxidative stress: MDA and GSH in brain tissue was restored after test drug treatments. Conclusion It may be concluded that Sirtuin is involved in mediation of memory and learning in neuronal oxidative damage in rodents.