Iso-α-Acids, Bitter Components in Beer, Suppress Inflammatory Responses and Attenuate Neural Hyperactivation in the Hippocampus.

Yasuhisa Ano,Kazuyuki Uchida,Misato Yoshikawa,Makoto Michikawa,Akihiko Takashima,Hiroyuki Nakayama,Yuta Takaichi

doi:10.3389/fphar.2019.00081

Abstract

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-α-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-α-acids on neural activity in Alzheimer’s disease model mice have not been investigated. Here, we demonstrated that short-term intake of iso-α-acids suppresses inflammation in the hippocampus and improves memory impairment even after disease onset. Importantly, we demonstrated that short-term administration of iso-α-acids attenuated the neural hyperactivation in hippocampus. In 6-month-old 5 × FAD mice exhibiting hippocampus inflammation and memory impairment, oral administration of iso-α-acids for 7 days reduced inflammatory cytokines, including MIP-1α and soluble Aβ and improved object memory in the novel object recognition test. In 12-month-old J20 mice, intake of iso-α-acids for 7 days also suppressed inflammatory cytokines and soluble Aβ in the brain. Manganese-enhanced magnetic resonance imaging (MEMRI) of hippocampi of J20 mice showed increased manganese compared with wild type mice, but iso-α-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-α-acids can suppress hippocampus inflammation even after disease onset and improve hyper neural activity in Alzheimer’s disease model mice.

Highlights

The rise in aging populations worldwide is accompanied by increasing rates of dementia and cognitive impairment, which are a burden to national healthcare systems as well as patients and their families
The present study demonstrated that short-term treatment of iso-α-acids as 7 days suppressed inflammation in the hippocampus and improved memory impairment in Alzheimer’s disease model mice, even after disease onset
We previously reported that iso-α-acids activate the peroxisome proliferator-activated receptor-γ (PPAR-γ) (Yajima et al, 2004) and that the PPAR-γ activation is involved in the suppression of microglial inflammation (Ano et al, 2017)

Summary

Introduction

The rise in aging populations worldwide is accompanied by increasing rates of dementia and cognitive impairment, which are a burden to national healthcare systems as well as patients and their families. Iso-α-Acids Attenuate Neural Hyperactivation in the Hippocampus reduce the risk of cognitive decline and the development of dementia. Our group previously demonstrated that long-term intake of iso-α-acids for 3 months, which are bitter components in beer, prevented Alzheimer’s pathology in a transgenic mouse model. Long-term administration of iso-α-acids is applicable for the preventive approaches, but the effects for the therapeutic approaches and for neural activity have not been elucidated. Previous study did not conclude that long-term administration of iso-α-acids suppressed the inflammation in the brain directly or as a result of the improvement of amyloid β (Aβ) deposition. To address these research gaps, in the present study, we examined the effects of short-term intake of iso-α-acids on brain inflammation and neural activity in hippocampus using the manganeseenhanced magnetic resonance imaging (MEMRI) in Alzheimer’s model mice

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Results

Conclusion