Quercetin mitigates scopolamine-induced memory dysfunction: impact on oxidative stress and cholinergic mechanisms.

Despite the promising neuroprotective activities of quercetin (QT), its' effect on cholinergic neurotransmission needs further elucidation. In this study, we explored the impact of QT on oxidative stress and cholinergic neurotransmission with emphasis on the possible involvement of choline acetyltransferase (ChAT) as a potential mechanism of QT on memory function at the hippocampal sub-regions and prefrontal cortex of mice brains. Mice were administered orally with QT (12.5 and 25 mg/kg) alone or in combination with SC (3 mg/kg, intraperitoneally) once daily for seven consecutive days. Thirty minutes after the last treatment, memory function was assessed using the Y-maze test. Levels of biomarkers of oxidative stress and acetylcholinesterase (AChE) activity were determined using a microplate reader. ChAT activity was determined by immunohistochemistry. QT pretreatment enhanced memory performance and reversed scopolamine (SC)-induced memory impairment in the Y-maze test. QT also reduced malondialdehyde and nitrite levels in mice brains. Glutathione levels were increased in mice brains as a result of QT administration. Levels of antioxidant enzymes (superoxide dismutase and catalase) were significantly increased in the mice brains, but AChE activity was reduced by QT. The activity of ChAT was significantly enhanced by QT in the hippocampal sub-regions and the prefrontal cortex of the mice brains. This study has shown that QT mitigated SC-induced memory dysfunction by inhibiting oxidative stress and AChE activity. Also, QT enhanced ChAT activity, particularly in the hippocampal sub-regions and the prefrontal cortex. These mechanisms, may be possible means through which QT improves memory performance.

Quercetin mitigates memory deficits in scopolamine mice model via protection against neuroinflammation and neurodegeneration.

AIMS: Neurodegenerative disorders like Alzheimer's disease (AD) are outcomes of neuroinflammatory processes that result in memory impairment. Quercetin (QT), a plant based flavonoid, has demonstrated notable effects against neurodegeneration and inflammation in models of dementia. However, the underlying mechanisms have not been well elucidated. This study evaluated the possible effects of QT against neuroinflammation and neurodegeneration in scopolamine (SC) induced memory impairment. MAIN METHODS: SC was used to induce memory loss in mice after which novel object recognition test (NORT) was used to assess memory function. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the brain tissues of the animals. Brain histology was carried out on the hippocampus (cornus ammonis 1, cornus ammonis 3 and dentate gyrus), and the prefrontal cortex. The population of healthy neuronal cells was counted, using ImageJ software. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was employed for the identification of cells undergoing apoptosis. KEY FINDINGS: QT reversed memory impairment in the NORT. Increases in TNF-α and IL-6 were attenuated by QT, and histology revealed that QT attenuated SC-induced cell degeneration and death in the hippocampal sub-regions and prefrontal cortex. QT diminished the population of dead cells in SC-treated mice, and also reversed the process of apoptosis induced by SC. SIGNIFICANCE: Findings from the study suggest that QT mitigates pro-inflammatory mediators and reverses neurodegeneration to restore memory function.