トコトリエノールによる神経保護作用の可能性に関する研究

抄録

Cognitive dysfunction is induced in vitamin E-deficient and normal old rats. Previously, we found neuronal apoptosis in the hippocampal CA1 region which plays an important role in cognitive function. In this point, however it is difficult to treatment of cognitive function because the neurons have already died. It is necessary to find early sign before induction of cell death in vitamin E-deficient and normal old rats. We found beads formation in the axon and dendrite as neuronal degeneration. This neurite degeneration was discovered in not only cell line model but also primary cultured cells. Furthermore, we found the induction of axonal degeneration in the hippocampal CA1 region of vitamin E-deficient and normal old mice using silver staining. Treatment with tocotrienols significantly inhibited hydrogen peroxide-induced neurite degeneration in neuro2a and granule cells. These results indicate that tocotrienols have neuroprotective function. Next, we examined the mechanism of induction of neurite degeneration in vitamin E-deficient and normal old mice. Treatment with 2,2'-azobis(2-methylpropion amide) dihydorochloride (AAPH), which is one of water-soluble free radical generators, induced neurite degeneration in neuro2a cells. The expression of collapsin response mediator protein (CRMP)-2 which plays a role in microtubule assembly decreased in the brain of vitamin E-deficient and normal old mice. Furthermore, autophagy function also attenuated in the brain of vitamin E-deficient and normal old mice. These alterations were improved by treatment with tocotrienols. These results show the possibility that one of the mechanisms of the neuroprotective effects of tocotrienols may be involved in their antioxidant and non-antioxidant functions.