Iso-α-Acids, Bitter Components in Beer, Suppress Inflammatory Responses and Attenuate Neural Hyperactivation in the Hippocampus
Iso-α-Acids, Bitter Components in Beer, Suppress Inflammatory Responses and Attenuate Neural Hyperactivation in the Hippocampus
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DOI：
10.3389/fphar.2019.00081
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发表时间：
2019-02-11
影响因子：
5.6
通讯作者：
Takashima, Akihiko
中科院分区：
文献类型：
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作者：
Ano, Yasuhisa;Yoshikawa, Misato;Takashima, Akihiko
由于全球老龄化人口的增长，对老年性认知功能减退和痴呆的预防和治疗需求很大。我们之前证明，长期摄入异阿尔法酸，在啮齿动物模型中预防阿尔茨海默氏症的病理。异阿尔法酸是啤酒中发现的一种从啤酒花中提取的苦味化合物。另一方面，异α-酸对阿尔茨海默病模型小鼠神经活动的影响还没有被研究。在这里，我们证明了短期摄入异阿尔法酸抑制了海马区的炎症，并改善了即使在疾病发作后的记忆损害。重要的是，我们证明了短期给予异阿尔法酸可以减轻海马区神经过度活跃的程度。在6个月大的表现为海马区炎症和记忆障碍的5×FAD小鼠中，口服7天的异阿尔法酸减少了炎症细胞因子，包括MIP-1α和可溶性Aβ，并在新的对象识别测试中改善了对象记忆。在12个月大的J20小鼠中，连续7天摄入异阿尔法酸也抑制了大脑中的炎性细胞因子和可溶性Aβ。与野生型小鼠相比，J20小鼠海马区的锰增强磁共振成像(MEMRI)显示锰含量增加，但异α-酸抵消了J20小鼠海马区，特别是海马区CA1和CA3区增加的MEMRI信号。综上所述，这些发现表明，即使在疾病发作后，短期摄入异阿尔法酸也可以抑制海马区炎症，并改善阿尔茨海默病模型小鼠的神经活动。
Due to the growth in aging populations worldwide, prevention and therapy for age-related cognitive decline and dementia are in great demand. We previously demonstrated that long-term intake of iso-alpha-acids, which are hop-derived bitter compounds found in beer, prevent Alzheimer's pathology in a rodent model. On the other hand, the effects of iso-alpha-acids on neural activity in Alzheimer's disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-alpha-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-alpha-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 x FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-alpha-acids for 7 days reduced inflammatory cytokines, including MIP-1 alpha and soluble A beta and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-alpha-acids for 7 days also suppressed inflammatory cytokines and soluble A beta in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-alpha -acids canceled this increased MEMRI signal in J20 mice, particularly in the hippocampus CA1 and CA3 region. Taken together, these findings suggest that short-term intake of iso-alpha-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer's disease model mice.