Potencial neuroprotetor do ácido tânico em modelo experimental de demência esporádica do tipo Alzheimer

Abstract

Alzheimer's Disease (AD) is a neurodegenerative disease without pharmacotherapy capable of reversing the neurodegenerative process once installed. In this sense the use of preventive strategies becomes relevant. Some polyphenolic compounds have been shown to positively influence the pathology of AD, so the aim of this study was to investigate the ability of tannic acid (TA) to prevent memory deficits and neurochemical alterations induced by intracerebroventricular (icv) administration of streptozotocin (STZ) in a model of Sporadic Dementia of Alzheimer’s Type (SDAT) in rats. Male Wistar rats, 60 day-old were divided into four groups: control, TA, STZ, and TA+STZ. Animals of TA and TA+STZ groups were treated by gavage with TA (30 mg/kg, b.w.) per 21 days and the others groups received vehicle (water). At the 22th day animals were submitted to stereotaxic surgery. The STZ and TA+STZ groups received bilateral icv injection of 5 μL of STZ (3 mg/kg, b.w.) and others received vehicle (citrate buffer). After recovery (3 days), treatment was reestablished and animals were evaluated in behavioral tests: Y-maze, object recognition and inhibitory avoidance task. Next, the animals were euthanized by decapitation and the cerebral cortex and hippocampus were used for biochemical, histological and molecular analysis. STZ induced learning and memory impairments in object recognition, Y-maze and inhibitory avoidance tests; however, TA was able to prevent these effects. In cerebral cortex and hippocampus, STZ induced an increase in acetylcholinesterase activity, reduced Na+, K+ -ATPase activity and induced oxidative stress increasing thiobarbituric acid-reactive substances, nitrites and reactive oxygen species levels and reducing the activity of antioxidant enzymes. Treatment with TA was able in prevent the major of these neurochemical alterations. Neuronal survival, neuroinflammation, expression of neurodegeneration marker SNAP-25 and modulation of the PI3K/Akt signaling pathway in the cerebral cortex were all evaluated. STZ promoted increase in neuronal death and in the levels of proinflammatory cytokines (IL-6 and TNF-α), and a reduction in PI3K-Akt signaling; TA was able to restore these changes. Neither STZ nor TA altered SNAP-25 expression or the levels of IL-12 and IL-4 in the cerebral cortex. In conclusion, TA prevented memory deficit, alterations in brain enzyme activities, oxidative damage, impaired PI3K-Akt signaling and protected against neuronal death and neuroinflammation in STZ-induced SDAT in rats proving to be potential therapeutic agents in the prevention of Sporadic Alzheimer’s Disease.