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Quercetin exerts neuroprotective effects through activation of PI3K/AKT/CREB/BDNF signaling pathway in double blow
Yating Yang1, Mengdie Li2, Yunxiao Liu3
1Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Ganzhou Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; Guangdong Mental Health Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
Objective:
Cognitive impairment represents a core clinical feature of schizophrenia, yet effective therapeutic interventions remain lacking. Given quercetin's demonstrated anti-inflammatory and neuroprotective properties, this study investigates its potential to ameliorate cognitive deficits in schizophrenia while elucidating the underlying mechanisms.
Methods:
A schizophrenia-like model was established through perinatal injection of MK-801 combined with social isolation. Behavioral assessments evaluated quercetin's antipsychotic potential and its effects on cognitive deficits in this model. Immunofluorescence quantified DCX, Nestin, and microglia populations in hippocampal tissue. Hippocampal neuron morphology was analyzed using H&E, Nissl staining and TUNEL staining. Western blot measured hippocampal expression levels of PI3K, p-PI3K, AKT, p-AKT, CREB, p-CREB, BDNF, PSD95, SYN, Bax, and Bcl-2.
Results:
Quercetin dose-dependently reduced the distance of spontaneous movement, the frequency of stereotyped behaviors, and prepulse inhibition in MK-SI model mice, while improving the recognition memory and spatial memory impairments in the MK-SI group. Quercetin activated the PI3K/AKT/CREB/BDNF signaling pathway, increased the expression of synaptic plasticity proteins SYN and PSD95 in the hippocampal tissues of MK-SI model mice, balanced the imbalance of Bax/Bax-2 in the hippocampal tissues of mice in the MK-SI group, and promoted neurogenesis. Additionally, quercetin suppressed hippocampal microglial activation in the model mice, attenuated proinflammatory cytokine release, and mitigated neuroinflammation, demonstrating comprehensive neuroprotective effects.
Conclusion:
Quercetin can improve cognitive impairment in schizophrenic mice, providing a theoretical basis for its future clinical application.
