Paeoniflorin improves cognitive dysfunction, restores glutamate receptors, attenuates gliosis and maintains synaptic plasticity in cadmium-intoxicated mice

Toxic metals exposed to the environment in industrial and agricultural production, such as cadmium (Cd), Plumbum (Pb) and aluminium (Al), are neurotoxic and harmful to brain functions such as learning and memory, and may contribute to neurological disease. In this study, we investigated the neuronal protective effects of Paeoniflorin (PF) in a mouse model of Cd poisoning that showed cognitive dysfunction. PF attenuated Cd-induced multi-organ damage and brain neurotoxicity, consistent with improved behavioral performances in mice. At the molecular level, Cd-induced toxicity attenuated the phosphorylation of glutamate receptors NMDAR2A, NMDAR2B, and GluR2, but increased the phosphorylation of GluR1. In addition, gliosis after Cd toxicity showed an increase in the number of IBA1 or GFAP-positive cells, which contrasted with the loss of neurons and synapses. However, PF treatment alleviated gliosis and maintained glutamate receptor and neuronal activity, as evidenced by the recovery of marker proteins MAP2, PSD95 and synaptophysin. Also, Cd-induced upregulation of CD68, a lysosomal protein that scavenges damaged cellular components in active microglia, was also restored by PF. In conclusion, PF is a potential neuroprotective natural product.