Tanshinone IIA Rescued the Impairments of Primary Hippocampal Neurons Induced by BV2 Microglial Over-Activation

Abstract

Activated microglia plays an important role in monitoring the microenvironment and prune neural process in healthy neural tissue, in order to maintain synaptic homeostasis. However, hyperactive microglia may release various cytotoxic factors and induce neuroinflammation, which cause neuronal damages leading to neurodegenerative diseases. Tanshinone IIA (TSA), an extract from traditional Chinese medicine, features potent anti-apoptotic and anti-inflammatory effects both in vitro and in vivo. But little is known on the effects of TSA on microglial-over-activation-induced neural impairments. In this study, by employing murine BV2 cell lines as well as the combinations of ELISA assay, immunostaining, western blotting analysis and RT-PCR, we found that TSA has the potential to exhibit anti-inflammatory effects. We hereby demonstrated that TSA rescued neural growth and development in the primary cultured hippocampal neurons from impairments caused by BV2 microglial over-activation insult. The results show that TSA attenuated the BV2 cell activation by lipopolysaccharide (LPS) stimulation through suppressing the NF-кB signal pathway. Also, conditioned mediums (CM) from TSA treated and activated BV2 cells protected against LPS-CM-induced neuronal death. Furthermore, TSA treatment could recover the inhibitory effects of LPS-CM on growth cone extension, neurite sprouting and outgrowth, as well as spinogenesis. Our findings support that TSA is capable of inhibiting BV2 cell over-activation thus has potential protective effects in the cultured hippocampal neurons. This study may lay a foundation for using TSA to restore cerebral injuries after severe neuroinflammation.