Kaempferol improves Pb-induced cognitive impairments via inhibiting autophagy

Kaempferol (Kam) is a flavonoid antioxidant found in fruits and vegetables, which was discovered as neuroprotective antioxidants. Lead (Pb), an environmental pollution, could induce learning and memory deficits. Nevertheless, little is known about the mechanisms underlying Kam actions in Pb-induced learning and memory deficits. In this study, we investigated the effects of Kam on Pb-induced cognitive deficits. Pb-exposed rats were treated with 50 mg/kg Kam from postnatal day (PND) 30 to PND 60. Then, Y-maze and Morris water maze have been used to detect the spatial memory in all groups of rats. Hematoxylin and eosin (HE) staining and Nissl staining were used to analyze the neuronal structure damages. The results found Kam treatment improved the learning and memory ability and alleviated hippocampal neuronal pathological damages. Besides, Kam could significantly reverse the synaptic transmission related protein expression including PSD95 and NMDAR2B. Further research found that Kam downregulated autophagy markers, P62, ATG5, Beclin1, and LC3-II. Furthermore, 3-MA, autophagy inhibitor, increased the levels of NMDAR2B and PSD95 in Pb-induced PC12 cells, indicating Kam alleviated Pb-induced neurotoxicity through inhibiting autophagy activation. Our results showed that Kam could ameliorate Pb-induced cognitive impairments and neuronal damages by decreasing Pb-induced excess autophagy accumulation.