베타아밀로이드로 유도된 신경세포 사멸과 기억력 손상에 대한 밀기울추출물의 보호효과

Abstract

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against <TEX>${\beta}$</TEX>-amyloid (<TEX>$A{\beta}$</TEX>)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against <TEX>$A{\beta}_{25-35}$</TEX>-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against <TEX>$A{\</TEX><TEX>beta}_{25-35}$</TEX>-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. <TEX>$A{\beta}_{25-35}$</TEX>-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from <TEX>$A{\beta}_{25-35}$</TEX>-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.