Quercetin alleviates Valproic Acid-Induced Autistic Features in mice via down-regulation of TLR4/NF-κB signaling pathway

Introduction: Autism spectrum disorder (ASD) is linked to stereotypical behavior and poor social skills. Quercetin (Qrct) has been shown to possess anti-inflammatory and antioxidant impacts.Objective: to demonstrate the underlying processes and the neuroprotective impact of Qrct in VPA-induced ASD.Material & methods: Thirty male Wister albino rats were split into three: control, VPA, and VPA+ Qrct. Following neurobehavioral testing, the rats were sacrificed, and the cerebellar gene expression of TLR4 and NF-kB was evaluated together with the measurements of cerebellar MDA, SOD, TNF-α, IL-6, IL-10, BDNF, and serotonin. Cerebellar and histopathological immunoreactions for Bax and NF-kB were performed. Results: While the VPA group's number of crossing slots in OFT, time of central crossing in OFT, cerebellar SOD, cerebellar IL-10, cerebellar BDNF, and cerebellar serotonin were dramatically decreased than those of the control, the VPA group's rearing frequency in OFT, time in the open arms of EPM, cerebellar MDA, cerebellar TNF-α, cerebellar IL-6 and cerebellar TLR4 and NF-kB gene expression dramatically increased than those of the control. Additionally, the VPA group's NF-kB and Bax cerebellar immunoreaction were dramatically increased than those of the control. Qrct significantly enhanced ASD caused by VPA.Conclusion: Qrct reduced VPA-induced ASD by down-regulation of the cerebellar TLR4/NF-kB pathway as well as anti-oxidant, anti-inflammatory, neurotropic, and antiapoptotic pathways.