Quercetin Attenuates Depressive- Like Behavior in a Rat Model of Alzheimer’s Disease: Involvement of Galectin-3 Signaling Pathway

Background and objectives: Clinical studies have consistently identified depression-related disorders as the most prevalent neuropsychiatric symptoms in Alzheimer’s disease (AD). Quercetin has garnered significant attention as a therapeutic approach for various neuropsychiatric conditions, particularly symptoms of depression in individuals. This study aimed to compare the neuroprotective effects of quercetin on depression-like behaviors and serum levels of anti-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and galectin (Gal)-3, in a rat model of AD. Methods: Forty-eight Wistar rats were categorized into six groups: control, sham, AD, quercetin 10, quercetin 25, and quercetin 100 mg/kg body weight through gavage for 8 weeks. The rat model of AD was induced by intra-cerebroventricular administration of streptozotocin (STZ; 4 mg/rat, bilaterally). Depressive-like behaviors were assessed using the forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT). Additionally, serum Gal-3 and TNF-α concentrations were measured. Results: STZ administration led to increased depression-related behaviors in OFT, EPM, and FST. Significant elevations in serum TNF-α, coupled with a decrease in Gal-3 concentrations in the hippocampus of AD rats, were observed. Remarkably, quercetin treatment reversed hippocampal cytokine concentrations in STZ-treated rats. Quercetin at the doses of 25 and 100 mg/kg significantly increased serum Gal-3 concentrations compared to other groups. Conclusion: The antidepressant effects of quercetin may be linked to its capacity to reduce inflammation and increase Gal-3 levels.