Effects Of Fullerenol On Hippocampal Neuron Viability And Learning And Memory In Rats

BACKGROUND:As a kind of functional water-soluble fullerene derivative, fullerenol has driven extensive applications in biomedical fields. Fullerenol is known to protect cells and tissues as well as to have other properties of antioxidant, antitumor and antivirus at certain lower concentrations, but may have potential toxicity which leads to cell death or apoptosis at higher concentrations. Because fullerene derivatives can effectively get through the lipid membrane and influence calcium homeostasis, the central nervous systems may be a target of fullerene and its derivatives. However, the effect of fullerenol on the nervous systems is not well understood. The present study intended to investigate the effects of fullerenol on hippocampal neuron viability and on learning and mormory in rats.METHODS:The research was carried out in Wistar rats. The effect of fullerenol on hippocampal neuron viability was investigated with primary cell cultrue, MTT cell proliferation and cytotoxicity assay, Hoechst33342/PI double stain and single cell gel electrophoresis techniques. The influence of fullerenol on learning and memory was studied with in vivo field potential recording, Morris water maze, Golgi staining and scanning electron microscopy.RESULTS:(1) Fullerenol at low concentrations (below25μM) significantly enhanced neuron viability, and fullerenol at high concentrations (above100μM) reduced neuron viability;(2) Fullerenol at low concentrations improved the survival rate of hippocampal neurons after lead exposure. Fullerenol at high concentrations induced neuronal DNA damage and increased Caspase protein content;(3) Fullerenol could change the level of redox in cultured hippocampal neurons;(4) Fullerenol (5mg/kg intraperitoneal injection) meliorated the ability to locate the hidden platform in water.(5) Fullerenol could repair the damage of learning and memory caused by lead exposure;(6) Fullerenol could not reduce the level of redox in rat hippocampus;(7) Fullerenol significantly increased the number of dendritic spines and prevented reduction in postsynaptic density from lead-exposure, indicating structural changes accompanying the functional improvments and repairements.CONCLUSION AND DISCUSSION:Fullerenol promotes hippocampal neuron viability and protects these cells from lead-induced damage at lower concetrations, but causes cell death at higher concentrations in rats. The concentration-dependent effects of fullerenol are mainly due to its physical properties and its influence on the reduction-oxidation pathway. Low dose of fullerenol can improve learning and memory and hold a repair capacity of damages caused by lead exposure in Wistar rats. The influences of fullerenol in vivo are due to the functional changes of neuron structure. In fact, the biological function of fullerenol is more complex than we thought. The present study may provide a theoretical basis for biological assessment and for biomedical applications of fullerenol in the neuroscience-related fields.