掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.archoralbio.2024.106013

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Taste buds contain 2 types of GABA-producing cells: sour-responsive Type III cells and glial-like Type I cells. The physiological role of GABA, released by Type III cells is not fully understood. Here, we investigated the role of GABA released from Type III cells using transgenic mice lacking the expression of GAD67 in taste bud cells (Gad67-cKO mice). Immunohistochemical experiments confirmed the absence of GAD67 in Type III cells of Gad67-cKO mice. Furthermore, no difference was observed in the expression and localization of cell type markers, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), gustducin, and carbonic anhydrase 4 (CA4) in taste buds between wild-type (WT) and Gad67-cKO mice. Short-term lick tests demonstrated that both WT and Gad67-cKO mice exhibited normal licking behaviors to each of the five basic tastants. Gustatory nerve recordings from the chorda tympani nerve demonstrated that both WT and Gad67-cKO mice similarly responded to five basic tastants when they were applied individually. However, gustatory nerve responses to sweet–sour mixtures were significantly smaller than the sum of responses to each tastant in WT mice but not in Gad67-cKO mice. In summary, elimination of GABA signalling by sour-responsive Type III taste cells eliminates the inhibitory cell–cell interactions seen with application of sour–sweet mixtures.

DOI： 10.1007/s00424-024-03007-x

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その他リンク： https://link.springer.com/article/10.1007/s00424-024-03007-x/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Social deficits are debilitating features of many psychiatric disorders, including autism. While time-intensive behavioral therapy is moderately effective, there are no pharmacological interventions for social deficits in autism. Many studies have attempted to treat social deficits using the neuropeptide oxytocin for its powerful neuromodulatory abilities and influence on social behaviors and cognition. However, clinical trials utilizing supplementation paradigms in which exogenous oxytocin is chronically administered independent of context have failed. An alternative treatment paradigm suggests pharmacologically activating the endogenous oxytocin system during behavioral therapy to enhance the efficacy of therapy by facilitating social learning. To this end, melanocortin receptor agonists like Melanotan II (MTII), which induces central oxytocin release and accelerates formation of partner preference, a form of social learning, in prairie voles, are promising pharmacological tools. To model pharmacological activation of the endogenous oxytocin system during behavioral therapy, we administered MTII prior to social interactions between male and female voles. We assessed its effect on oxytocin-dependent activity in brain regions subserving social learning using Fos expression as a proxy for neuronal activation. In non-social contexts, MTII only activated hypothalamic paraventricular nucleus, a primary site of oxytocin synthesis. However, during social interactions, MTII selectively increased oxytocin-dependent activation of nucleus accumbens, a site critical for social learning. These results suggest a mechanism for the MTII-induced acceleration of partner preference formation observed in previous studies. Moreover, they are consistent with the hypothesis that pharmacologically activating the endogenous oxytocin system with a melanocortin agonist during behavioral therapy has potential to facilitate social learning.

DOI： 10.1016/j.neuropharm.2024.109848

PubMed

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記述言語：英語  

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and variation in its receptor gene (Oxtr) is associated with divergent social phenotypes. The cellular mechanisms connecting Oxtr genotype to social phenotype remain obscure. We exploit an association between Oxtr polymorphisms and striatal-specific OXTR density in prairie voles to investigate how OXTR signaling influences the brain transcriptome. We discover widespread, OXTR signaling-dependent transcriptomic changes. Interestingly, OXTR signaling robustly modulates gene expression of C-type lectin-like receptors (CTLRs) in the natural killer gene complex, a genomic region associated with immune function. CTLRs are positioned to control microglial synaptic pruning; a process important for shaping neural circuits. Similar relationships between OXTR RNA and CTLR gene expression were found in human striatum. These data suggest a potential molecular mechanism by which variation in OXTR signaling due to genetic background and/or life-long social experiences, including nurturing/neglect, may affect circuit connectivity and social behavior.

DOI： 10.1101/2023.10.26.564214

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cephalic-phase insulin release (CPIR) occurs before blood glucose increases after a meal. Although glucose is the most plausible cue to induce CPIR, peripheral sensory systems involved are not fully elucidated. We therefore examined roles of sweet sensing by a T1R3-dependent taste receptor and sugar sensing by oral glucose transporters in the oropharyngeal region in inducing CPIR. Spontaneous oral ingestion of glucose significantly increased plasma insulin 5 min later in wild-type (C57BL/6) and T1R3-knockout mice, but intragastric infusion did not. Oral treatment of glucose transporter inhibitors phlorizin and phloretin significantly reduced CPIR after spontaneous oral ingestion. In addition, a rapid increase in plasma insulin was significantly smaller in WT mice with spontaneous oral ingestion of nonmetabolizable glucose analog than in WT mice with spontaneous oral ingestion of glucose. Taken together, the T1R3-dependent receptor is not required for CPIR, but oral glucose transporters greatly contribute to induction of CPIR by sugars.

DOI： 10.1186/s12576-023-00875-3

PubMed

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開催年月日： 2024年11月2日 - 2024年11月4日

記述言語：日本語   会議種別：口頭発表（一般）  

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開催年月日： 2024年11月2日 - 2024年11月4日

記述言語：日本語   会議種別：ポスター発表  

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開催年月日： 2024年9月11日 - 2024年9月13日

記述言語：英語   会議種別：ポスター発表  

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開催年月日： 2023年11月25日 - 2023年11月26日

記述言語：英語   会議種別：口頭発表（一般）  

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開催年月日： 2023年10月27日 - 2023年10月28日

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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