Lovastatin Potentiates the Function of α7-Nicotinic Acetylcholine Receptors.

Background/

Objectives

Statins are currently one of the most commonly used cholesterol-lowering drugs. In recent years, in addition to their well-known effects on the cardiovascular system, statins have been shown to exert beneficial effects in the progression of various neuropsychiatric and neurodegenerative diseases.

Methods

In this study, the effects of lovastatin on the function of α7-nicotinic acetylcholine (nACh) receptors expressed in rat hippocampus and Xenopus oocytes were investigated.

Results

In whole-cell patch clamp studies in hippocampal neurons, 21-day chronic (20 mg/kg), but not acute (20 min), lovastatin treatment caused significant potentiation of choline (a selective agonist for α7 nACh receptors)-induced currents and choline-induced increases in GABAA receptor-mediated currents. Further studies in Xenopus oocytes expressing human α7-nACh receptors indicated that 72 h pretreatment with lovastatin caused a significant increase in α7-nACh receptor function with an EC50 value of 296 nM. Other statins, such as simvastatin and pravastatin, also potentiated α7-nACh receptors. Potentiation by lovastatin treatment was associated with a significant decrease in oocyte cholesterol content and was diminished by Go6983, an inhibitor of protein kinase C (PKC), suggesting that both decreased cholesterol levels and activation of PKC are involved in statin potentiation of α7-nACh receptors.

Conclusions

In conclusion, our findings indicate that chronic lovastatin treatment potentiates the function of α7-nACh receptors in hippocampal neurons and in Xenopus oocytes expressing human α7-nACh receptors and provides important insights that could guide future efforts to design novel drugs targeting α7-nACh receptors.