Program

PO1-1-53

Iso-α-acids, bitter components in beer, suppress inflammation and neural activation in the hippocampus of Alzheimer's model mice, resulting in cognitive improvement

[Speaker] Yasuhisa Ano:1
[Co-author] Yuka Yoshino:2, Misato Yoshikawa:3, Kazuyuki Uchida:2, Hiroyuki Nakayama:2, Akihiko Takashima:3
1:Research Laboratories for Health Science & Food Technologies, Kirin Company, Limited, Japan, 2:Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan, 3:Faculty of Science, Gakushuin University, Japan

<Background>
Our group previously reported that iso-α-acids, bitter components in beer, display preventive effects against Alzheimer's pathology using 5xFAD model mice (Ano et al., 2017, J. Biol. Chem.). Long-term intakes of iso-α-acids before the onset of the pathology suppress microglial inflammation and prevent cognitive decline in the mice, however, therapeutic effects of iso-α-acids after the onset have not been elucidated. It is also reported that such inflammation in the hippocampus is caused by Aβ deposition, makes neurons excessively activated and finally induces cognitive decline. In the present study, therapeutic effects of iso-α-acids against Alzheimer's pathology after the onset are investigated using the 5xFAD and J20 model mice.

<Methods>
Six-month-old 5xFAD and 12-month-old J20 transgenic mice were orally administered with 0 or 1 mg/kg iso-α-acids for 7 days. Cognitive functions in 5xFAD mice were evaluated using a novel object recognition test (NORT), and neural activities in J20 mice explored in the novel open field for 30 min x 4 sets were examined using manganese-enhanced magnetic resonance imaging (MEMRI) with intraperitoneal injection of MnCl2. Aβ and cytokines in the hippocampus and cerebral cortex were measured by ELISA.

<Results>
Intakes of iso-α-acids significantly increased novel object approaching time in 5xFAD mice. Therefore, intakes of iso-α-acids improve hippocampus-dependent memory functions even after the disease onset. MEMRI examination revealed the increased accumulation of Mn especially in the hippocampus and cerebral cortex of untreated control J20 mice compared with that of wild-type mice. However, Mn accumulation of J20 mice treated with iso-α-acids was almost same, especially in the hippocampal CA1 region, compared with that of wild type mice. The amounts of soluble Aβ1-42, TNF-α and MIP-1α in the hippocampus of 5xFAD and J20 mice treated with iso-α-acids were significantly reduced compared with those in untreated transgenic mice.

<Conclusions>
The present study suggests that iso-α-acids intakes not only before but also after the onset of Alzheimer's pathology suppress inflammation caused by Aβ deposition and regulate neuronal activation in the hippocampus, resulting in the cognitive improvement.
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