Anti-inflammatory treatment with β-asarone improves impairments in social interaction and cognition in MK-801 treated mice

The aim of this study investigates whether β-asarone can improve cognition deficits in dizocilpine (MK-801) treated mice. Six-week-old male C57BL/6 mice were divided into four groups: control group (CON), MK-801-treated group (MK-801), MK-801 plus β-asarone group (MK-801+β-asa) and β-asarone group (β-asa). Behavioral tests, including sociability test, open field test (OPT) and Morris water-maze (MWM), were performed. Extracellular field excitatory postsynaptic potentials were recorded in the hippocampal dentate gyrus (DG) region. Western blot was employed to measure the expression of cognitive function-associated proteins and pro-inflammatory cytokines in the hippocampus. Immunofluorescence was performed to assess the microglial activation in the hippocampus DG region. The data show that social interactions and spatial learning and memory were impaired by MK-801. However, β-asarone significantly mitigated the impairments. Furthermore, it was found that MK-801 aggravated the hyperactivity and anxiety-like behavior, but β-asarone alleviated them. Moreover, β-asarone alleviated the impairments of hippocampal synaptic plasticity and enhanced the expression of hippocampal synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) in MK-801-treated mice. In addition, it suppressed the expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), inducible nitric oxide synthase (i-Nos) and cyclo-oxygenase-2 (COX-2) expression in MK-801-treated mice. The results suggest that β-asarone improved the impairment of cognition and synaptic plasticity possibly through modulating the excess release of pro-inflammatory cytokines and microglia activation in MK-801-treated mice.