UNC-CH Division of Clinical Laboratory Science, University of North Carolina Chapel Hill, Chapel Hill, NC, USA.
Tarleton State University, Stephenville, TX, USA.
Biol Res Nurs. 2025 Jan;27(1):71-80. doi: 10.1177/10998004241270079. Epub 2024 Aug 21.
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.
脂质代谢失衡与神经退行性疾病有关。降胆固醇药物，如他汀类药物，因其可能具有改善或预防与神经退行性相关的认知能力下降的潜力而受到特别关注。然而，关于他汀类药物对认知功能的实际影响存在很大争议。本研究旨在探讨匹伐他汀对海马突触发生的影响，因为海马对于记忆形成至关重要。我们还评估了匹伐他汀对海马自身合成的局部海马雌激素的影响及其对脑源性神经营养因子 (BDNF) 的影响。使用海马细胞系 H19-7，我们发现暴露于匹伐他汀的海马神经元中突触后密度蛋白 95（psd-95）这种突触标记物的数量明显减少。经匹伐他汀处理的神经元还表现出局部雌激素产生减少，其 BDNF mRNA 的表达减少。这些结果表明，他汀类药物通过限制局部雌激素的产生来降低海马神经元形成突触的能力。由于海马中的神经连接对于记忆形成至关重要，我们的发现表明他汀类药物可能会损害认知功能的药物。
