Quercetin Exhibits α7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents
| Autor: | Niraj Kumar Singh, Debapriya Garabadu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
endocrine system diseases
General Neuroscience Pharmacology Toxicology medicine.disease medicine.disease_cause Neuroprotection Acetylcholinesterase Choline acetyltransferase chemistry.chemical_compound Mitochondrial toxicity chemistry medicine Cholinergic heterocyclic compounds Quercetin Oxidative stress Acetylcholine medicine.drug |
| Zdroj: | Neurotoxicity Research. 39:1859-1879 |
| ISSN: | 1476-3524 1029-8428 |
| Popis: | The objective of the present study was to investigate the α7nAChR-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 α7nAChRs 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 α7nAChR/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. |
| Databáze: | OpenAIRE |
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