The Effect of Statin Treatment on Synaptogenesis in the Hippocampus.

Abstract

Deranged lipid homeostasis has been implicated in neurodegenerative diseases. Cholesterol reducing compounds such as statins have received special attention for the possibility that they may be able to ameliorate or prevent cognitive loss associated with neurodegeneration. However, there is much dissension concerning the actual effect of statins on cognitive function. The aim of this study is to investigate the effects of pitavastatin on hippocampal synaptogenesis because the hippocampus is crucial for memory formation. We also evaluated the effects of pitavastatin on local hippocampal estrogen synthesized in the hippocampus itself and its effect on Brain-Derived Neurotrophic Factor (BDNF). Using a hippocampal cell line, H19-7, we found that hippocampal neurons exposed to pitavastatin demonstrate a significant reduction in the synaptic marker postsynaptic density protein 95 (psd-95). The pitavastatin treated neurons also exhibited decreased production of local estrogen and their expression of BDNF mRNA was decreased. These results suggest that statins reduce the ability of hippocampal neurons to form synapses by restricting the production of local estrogen. Because neural connections in the hippocampus are crucial for memory formation, our findings implicate statins as medications that may compromise cognitive function.