Ang(1-7) exerts Nrf2-mediated neuroprotection against amyloid beta-induced cognitive deficits in rodents.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits in an individual. Ang(1-7) exhibits neuroprotection against amyloid beta (Aβ)-induced mitochondrial dysfunction and neurotoxicity in experimental conditions. Further, Ang(1-7) also exhibits nrf2-mediated antioxidant activity in experimental conditions. However, its therapeutic role on nrf2-mediated mitochondrial function is yet to be established in the Aβ-induced neurotoxicity. The experimental dementia was induced in the male rats by intracerebroventricular administration of Aβ(1-42) on day-1 (D-1) of the experimental schedule of 14days. Ang(1-7) was administered once daily from D-1 toD-14 to the Aβ-challenged rodents. Ang(1-7) attenuated Aβ-induced increase in escape latency and decrease in the time spent in the target quadrant during Morris water maze and percentage of spontaneous alteration behavior during Y-maze tests in the rats. Further, Ang(1-7) attenuated Aβ-induced cholinergic dysfunction in terms of decrease in the level of acetylcholine and activity of choline acetyltransferase, and increase in the activity of acetylcholinesterase, and increase in the level of Aβ in rat hippocampus, pre-frontal cortex and amygdala. Furthermore, Ang(1-7) reversed Aβ-induced decrease in the mitochondrial function, integrity and bioenergetics in all brain regions. Additionally, Ang(1-7) attenuated Aβ-induced increase in the extent of apoptosis and decrease in the level of heme oxygenase-1 in all selected brain regions. Trigonelline significantly abolished the therapeutic effectiveness of Ang(1-7) on Aβ-induced alterations in the behavioral, neurochemicals and molecular observations in the animals. Ang(1-7) may exhibit nrf2-mediated neuroprotection in these rodents. Hence, Ang(1-7) could be a potential therapeutic option in the pharmacotherapy of AD.