Soy Isoflavone Alleviates Aβ1-42-Induced Impairment of Learning and Memory Ability Through the Regulation of RAGE/LRP-1 in Neuronal and Vascular Tissue

Yuan-Di      Xi; Xiao-Ying      Li; Juan      Ding; Huan-Ling      Yu; Wei-Wei      Ma; Lin-Hong      Yuan; Jian      Wu; Rong      Xiao

Abstract

The neuroprotective properties of soy isoflavone (SIF) have been demonstrated by our previous studies and others, but its potential mechanism is not clear. Because of the key role of neurovascular dysfunction in the pathogenesis of Alzheimer's disease (AD), we hypothesized neurovascular tissue might be one neuroprotective target of SIF. In the present study, learning and memory ability, β-amyloid (Aβ) expressions both in neurovascular tissue and plasma, the receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein (LRP)-1, nuclear factor-κB p65 (NF-κB p65), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expressions in neurovascular tissue were measured in Wistar rats following lateral cerebral ventricle administration of Aβ1-42 by miniosmotic pump with or without intragastric administration of SIF from 14 days before surgery to the end of experiment. The results showed that SIF could improve the impairment of learning and memory of rats induced by Aβ1-42, maintain Aβ homeostasis in brain, regulate the disordered expressions of RAGE/LRP-1 and restrain RAGE related NF-κB and inflammatory cytokines activation in neurovascular structure. These results suggested that SIF could protect Aβ-impaired learning and memory in rats, and its mechanism might be associated with the regulation of vascular Aβ transportation and vascular inflammatory reaction.

Keywords: Soy isoflavone, β-amyloid peptide 1-42, learning and memory ability, RAGE, LRP-1, NF-κB, neurovascular protection

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