Matured hop bitter acids improve spatial working and object recognition memory via nicotinic acetylcholine receptors

Fukuda, Toshio; Ayabe, Tatsuhiro; Ohya, Rena; Ano, Yasuhisa

doi:10.1007/s00213-019-05263-7

Cited by 11 publications

(10 citation statements)

References 47 publications

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“…To improve clinical practice, novel (complementary) treatments should target this phenotype directly, for example via 1) behavioral interventions - such as targeted memory reactivation (117, 118), behavioral tagging (118, 119), reconsolidation updating (118) and reminders (120) - that tap into endogenous encoding and retrieval processes; 2) cognitive training that enhances learning and memory strategies (121, 122); 3) physical exercise - like cardiovascular exercise (123–126) and balance training (127) - that stimulates the hippocampal memory system; 4) sleep interventions that enhance slow-wave sleep (128); 5) neurofeedback training that improves prefrontal cortex-hippocampus connectivity (129); or 6) pharmacotherapy that targets neurotransmitter systems (e.g. serotonin (130), dopamine (131), choline (132, 133)) or modulates neuronal processes (e.g. neurogenesis (134), neuro-inflammation (134), or neuronal damage (126)).…”

Section: Discussionmentioning

confidence: 99%

Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies

Sep

Geuze

Joëls

2021

Preprint

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Background. Current evidence-based treatments for post-traumatic stress disorder (PTSD) are efficacious in only part of PTSD patients. Therefore, novel neurobiologically-informed approaches are urgently needed. Clinical and translational neuroscience point to altered learning and memory processes as key in (models of) PTSD psychopathology. We extended this notion by clarifying at a meta-level i) the role of information valence, i.e. neutral versus emotional/fearful, and ii) comparability between clinical and preclinical phenotypes. We hypothesized that, cross-species, neutral versus emotional/fearful information processing is, respectively, impaired and enhanced in PTSD. Methods. This preregistered meta-analysis involved a literature search on PTSD+Learning/Memory+Behavior, performed in PubMed. First, the effect of information valence was estimated with a random-effects meta-regression. Then sources of variation were explored with a random forest-based analysis. Results. The analyses included 92 clinical (N=6732 humans) and 182 preclinical (N=6834 animals) studies. A general impairment of learning, memory and extinction processes was observed in PTSD patients, regardless of information valence. Impaired neutral learning/memory and fear extinction were also present in animal models of PTSD. Yet, PTSD enhanced fear/trauma memory in preclinical studies and impaired emotional memory in patients. Clinical data on fear/trauma memory was limited. Mnemonic phase and valence explained most variation in rodents but not humans. Conclusions. Impaired neutral learning/memory and fear extinction show very stable cross-species PTSD phenotypes. These could be targeted for novel PTSD treatments, building on neurobiological animal studies. We argue that seemingly cross-species discrepancies in emotional/fearful memory deserve further study; until then animal models targeting this phenotype should be applied with care.

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Section: Discussionmentioning

confidence: 99%

Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies

Sep

Geuze

Joëls

2021

Preprint

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“…A clinical trial showed that supplements with MHBAs improved cognitive function in older adults with subjective cognitive decline 26 . We have previously shown that MHBAs are associated with the vagus nerve and nicotinic acetylcholine receptors to improve cognitive function 22,23 ; however, the mechanisms underlying the effects of MHBAs on cognitive decline have not been entirely investigated. In the current study, we found that MHBAs prevented the inflammation-related cognitive decline and that the β-tricarbonyl moiety, which is common in the structure of MHBAs and IAAs, contributed to these effects via the activation of the vagus nerve.…”

Section: Discussionmentioning

confidence: 99%

“…We previously found that matured hop-derived bitter acids (MHBAs) activate the vagus nerve and noradrenergic system in the brain, thus improving memory impairment 22 , 23 . MHBAs are also derived from α- and β-acids and show mild bitterness 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

Hop bitter acids containing a β-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system

Ano

Ohya

Yamazaki

et al. 2020

Sci Rep

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The prevention of age-related cognitive decline and dementia is becoming a high priority because of the rapid growth of aging populations. We have previously shown that hop bitter acids such as iso-α-acids (IAAs) and matured hop bitter acids (MHBAs) activate the vagus nerve and improve memory impairment. Moreover, supplements with MHBAs were shown to improve memory retrieval in older adults. However, the underlying mechanisms have not been entirely elucidated. We aimed to investigate the effects of MHBAs and the common β-tricarbonyl moiety on memory impairment induced by the activation of microglia and the loss of the noradrenergic system. MHBAs and a model compound with β-tricarbonyl moiety were administered to LPS-inoculated mice and 5 × FAD Alzheimer’s disease (AD) model mice, following the evaluation in behavioral tests and microglial activation. To evaluate the association of noradrenaline with MHBAs effects, mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin that selectively damages noradrenergic projections from the locus coeruleus, were subjected to the behavioral evaluation. MHBAs reduced brain inflammation and improved LPS-induced memory impairment. A model compound possessing the β-tricarbonyl moiety improved the LPS-induced memory impairment and neuronal loss via the vagus nerve. Additionally, the protective effects of MHBAs on memory impairment were attenuated by noradrenaline depletion using DSP-4. MHBAs suppressed the activation of microglia and improved the memory impairment in 5 × FAD mice, which was also attenuated by noradrenaline depletion. Treatment with MHBAs increased cholecystokinin production from the intestinal cells. Generally, cholecystokinin activates the vagal nerve, which stimulate the noradrenergic neuron in the locus ceruleus. Taken together, our results reveal that food ingredients such as hop bitter acids with a β-tricarbonyl moiety suppress microglial activation and improve memory impairment induced by inflammation or AD pathology via the activation of the gut-brain axis and noradrenergic system. Supplements with hop bitter acids, including MHBAs, might be a novel approach for the prevention of cognitive decline and dementia.

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“…Our preclinical study showed that MHBA improved depressive-like behavior in mice after a 7-day administration . In addition, other in vivo studies of ours indicated that the possible mechanism of MHBA is to increase neurotransmitters, such as norepinephrine or acetylcholine (Ayabe et al, 2018;Fukuda, Ayabe, et al, 2019). Therefore, we hypothesized the short-term effects of MHBA and set the length of the treatment period at 3 weeks, including each 7-day evaluation of the effects of the intervention.…”

Section: Methodsmentioning

confidence: 99%

Effect of non‐alcoholic beer containing matured hop bitter acids on mood states in healthy adults: A single‐arm pilot study

Fukuda

Akiyama

Takahashi³

et al. 2021

Nursing & Health Sciences

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This study aimed to investigate the effect of non-alcoholic beer containing matured hop bitter acids on mood states among healthy adults older than 20 years. This study was an open-label longitudinal intervention design in which each participant served as their control. For 3 weeks, we evaluated the effect of non-alcoholic beer containing 35 mg of matured hop bitter acids on mood, sleep quality, and work performance. The data of 97 participants (age range: 23-72 years, median age: 42) were analyzed. After the intervention, we found that matured hop bitter acids significantly improved total mood state, including anxiety, depression, fatigue, and vigor, compared with the baseline. Furthermore, sleep quality and absolute presenteeism were significantly improved after the intervention compared with the baseline. The present exploratory study suggested that 3-week supplementation with matured hop bitter acids improved mood and peripheral symptoms in persons of a wide range of ages.Although further investigation is needed, the findings suggested that non-alcoholic beer in daily life might become a choice for maintaining mood states.

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Matured hop bitter acids improve spatial working and object recognition memory via nicotinic acetylcholine receptors

Cited by 11 publications

References 47 publications

Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies

Impaired learning, memory, and extinction in posttraumatic stress disorder: translational meta-analysis of clinical and preclinical studies

Hop bitter acids containing a β-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system

Effect of non‐alcoholic beer containing matured hop bitter acids on mood states in healthy adults: A single‐arm pilot study

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