HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities and memory. Chemokine CC motif ligand 2 (CCL2) is elevated in cerebrospinal fluid (CSF), and has been believed to contribute to HAND. Previous studies by our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) and causes nerve cell damage. However, there are few drugs currently available to treat nerve damage that is caused by CCL2. Panax notoginseng saponins (PNS) are isolated from Panax notoginseng and benefit the human body in various ways, including the neuroprotective effect. However, the protective effect of PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found that PNS improved CCL2-induced learning and memory impairment, and inhibited CCL2-induced cell death. These effects may be due to inhibiting over-activation of NMDA receptors by alleviating the dysfunction of glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was found to attenuate cell inflammation. Additionally, PNS pretreatment evidently inhibited apoptotic pathways by reducing the Bax/BCL-2 ratio and caspase-3, 8, 9 expressions. In conclusion, this study demonstrates that PNS provides substantial neuroprotection against CCL2-induced neurotoxicity, and may be a novel therapeutic agent in CCL2-induced HAND or other neurodegenerative diseases.
Keywords: CCL2; HIV-associated neurocognitive disorder; PNS; apoptosis; inflammation; oxidative stress.
Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.