p-Hydroxybenzyl Alcohol Prevents Memory Deficits by Increasing Neurotrophic Factors and Decreasing Inflammatory Factors in a Mice Model of Alzheimer’s Disease

Abstract

p-hydroxybenzyl alcohol (HBA) is one of the major components of Gastrodia elata Blume (GEB) phenolic compound. HBA has been reported to have a protective effect on amyloid-β (Aβ) induced cell death. However, the systemic effects and the detail molecular mechanism of HBA in Alzheimer’s disease (AD) animal models is not clear. In this study, we revealed the protective effects and the potential mechanisms of HBA on the impairments of cognitive function induced by soluble Aβ oligomers. Our results showed that HBA prevented neuronal cells death in a dose-dependent manner. The working memory and the spatial memory were significantly lower in AD model mice. HBA treatment prevented the memory deficits of the AD mice. HBA treatment significantly prevented the decreased spine density and decreased expression levels of synaptic proteins induced by Aβ₄₂. In addition, both mRNA levels and protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the Aβ₄₂-treated mice were decreased, the decreases were prevented by HBA treatment. The expression levels of TNF-α and IL-1β were increased by Aβ₄₂ treatment and the increase can be prevented by the HBA treatment. Moreover, HBA prevents the decreases in the level of nuclear erythroid 2 p45-related factor 2 (Nrf2) induced by Aβ₄₂ in hippocampal. Thus, we predict that HBA might prevent Aβ₄₂ oligomer-induced synapse and cognitive impairments through multiple targets including increasing Nrf2, increasing neurotrophic factors and decreasing inflammatory factors. Our study provided novel insights into the cellular mechanisms for the protective effects of HBA on AD.