Quercetin Exhibits ?7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents

Abstract

The objective of the present study was to investigate the ?7nAChR-mediated Nrf2-dependant protective activity against streptozotocin (STZ)-induced brain mitochondrial toxicity in Alzheimer�s disease (AD)-like rats. STZ (3�mg/kg) was injected through an intracerebroventricular route to induce AD-like dementia. Repeated Quercetin (50�mg/kg, i.p.) administration attenuated cognitive impairments in the STZ-challenged animals during Morris water-maze and Y-maze tests. Quercetin significantly mitigated the STZ-induced increase in cholinergic dysfunction, such as the increase in acetylcholinesterase activity, decrease in acetylcholine level, and activity of choline acetyltransferase, and increase in amyloid-beta aggregation and mitochondrial toxicity in respect of mitochondrial bioenergetics, integrity, and oxidative stress in memory-challenged rat hippocampus, prefrontal cortex and, amygdala. Further, Quercetin significantly attenuated STZ-induced reduction in the ?7nAChRs and HO-1 expression levels in the selected rat brain regions. On the contrary, trigonelline (10�mg/kg, i.p.) and methyllycaconitine (2�mg/kg; i.p.) abolished the neuroprotective effects of Quercetin against STZ-induced behavioral, molecular, and biochemical alterations in the AD-like animals. Hence, Quercetin exhibits ?7nAChR/Nrf2/HO-1-mediated neuroprotection against STZ-challenged AD-like animals. Thus, Quercetin could be considered as a potential therapeutic option in the management of AD. Graphical Abstract: [Figure not available: see fulltext.] � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.