Dried bonito broth improves cognitive function via the histaminergic system in mice

: Bonito extract, i.e., dried bonito broth (DBB), has been reported to counteract mental fatigue and to increase performance in a simple calculation task, but the mechanism by which DBB increases task performance is not known. The brain neurotransmitter histamine is biosynthesized only from histidine in the tuberomammillary nucleus. Histamine neurons are projected to almost all areas of the cerebral cortex, and histamine has various behavioral and neurobiological functions, particularly in recognition memory. Here we used a mouse model to investigate the effects of the oral ingestion of DBB, which contains abundant histidine, as well as the ingestion of histidine on cognitive function. In a retention trial of novel object recognition test, the administration of 1.6 g/kg of DBB and 500 mg/kg of histidine significantly increased the animals' exploratory behavior toward a novel object, and that these agents significantly increased the spontaneous alternation behavior ratio in a Y-maze under conditions of scopolamine-induced amnesia, which induced learning and memory impairment. These results suggested the improvement of spatial short-term working memory in a scopolamine amnesia model, as well as the strengthening of visual cognitive function by a single ingestion of DBB and histidine. Interestingly, the administration of αFMH, which is an inhibitor of histamine biosynthesis, eliminated the increase in the spontaneous alternation behavior ratio by DBB ingestion in the scopolamine-induced amnesia model, suggesting that DBB may improve working memory impairment via activation of the histaminergic neuron system.