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  • Histamine modulates an attentional state which might affect

    2022-06-30

    Histamine modulates an attentional state, which might affect performances in the object recognition test. Indeed, systemic injection of H3 receptor inverse agonists enhances the attentional state (41). However, the memory recovery in our study is unlikely to be due to the enhanced attentional state. First, local injection of thioperamide into the PRh enhanced retrieval of forgotten memories. Second, intra-PRh injection of an H2 receptor antagonist blocked the retrieval-enhancing effect of the systemic thioperamide treatment. Third, systemic thioperamide injection did not affect general exploration or locomotor activity. Moreover, betahistine treatment did not alter attention in the human symbol coding task. Histamine H3 receptor is a promising target for treating cognitive dysfunction. Accordingly, previous studies examined effects of histamine H3 receptor inverse agonists on human learning and memory but found little effect 16, 17, 18. The drug effects may depend on dose, task difficulty, and memory type. First, we employed 108 mg betahistine mesilate, which is about seven times as much as a typical single dose, because we estimated that this dose is required to achieve the concentration of 1 nM betahistine, which is necessary for maximal H3 receptor activation. Second, in the object recognition memory task, betahistine treatment enhanced retrieval performance of items that are more difficult to remember and in subjects with poorer performance, possibly through stochastic resonance as discussed above. Third, object recognition memory was sensitive to betahistine treatment, whereas paired-associate memory and working memory were not affected by the treatment. However, we do not exclude the possibility that H3 receptor inverse agonists affect other types of memory because histamine neurons send fiber projections to nearly all parts of the PFI 3 mg and because H2 and H3 receptors are distributed in many brain regions (3). In conclusion, we propose central histamine signaling as a potential target for reactivating forgotten object memories. Betahistine has an advantage of high safety (42); however, it also has disadvantages, including mixed inverse agonism/agonism and low efficacy (43). Currently, several new histamine H3 receptor antagonists or inverse agonists are being developed 44, 45, 46. These new drugs may improve memory retrieval impairments observed in various neuropsychiatric disorders.
    Acknowledgments and Disclosures This work was supported by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (C) (Grant No. 16K06989 [to HNom]), Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research on Innovative Areas “Mental Time” (Grant No. 16H01500 [to HNom] and Grant No. 25119004 [to YI]), “Memory Dynamism” (Grant No. 16H01267 [to HNom]), “Brain Information Dynamics” (Grant No. 18H05109 [to HNom]), “Evolinguistic” (Grant No. 18H05056 [to HNom]), “Prediction and Decision Making” (Grant No. 23120009 [to HT]), “AI and Brain Science” (Grant No. 16H06572 [to HT]), and “Chronogenesis” (Grant No. 18H05525 [to YI]), the Strategic Research Program for Brain Sciences in the “Development of BMI Technologies for Clinical Application” (to YI and HT), SENSHIN Medical Research Foundation (Grant No. 17:2-37 [to HNom]), Suzuken Memorial Foundation (Grant No. 17-082 [to HNom]), Takeda Science Foundation (to HNom), Akiyama Life Science Foundation (to HNom), Human Frontier Science Program (Grant No. RGP0019/2016 [to YI]), and Japan Science and Technology Agency Exploratory Research for Advanced Technology (Grant No. JPMJER1801 [to YI]).
    Introduction The microbiota on mucosal surfaces is increasingly being recognised to play an essential role in host development and in particular for inducing immune homeostatic networks. In addition to the taxonomic diversity of the microbiota, its metabolic activity has profound effects on the induction of immune tolerance [1, 2, 3]. Accumulating evidence suggests that certain bacterial strains and their associated metabolites may provide disease protective signals while other bacterial strains may stimulate aggressive and tissue damaging immune responses. Thus, the activity of the mammalian immune system seems to be governed by the balance between symbiotic and pathogenic factors derived from our microbial inhabitants [].