Kamata, A. | Search bioRxiv

bioRxiv2023

A method for evaluating hunger and thirst in monkeys by measuring blood ghrelin and osmolality levels

Hunger and thirst drive animals consumption behavior and regulate their decision-making regarding rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and related the thirst states to risky decisions for fluid rewards. However, hunger assessments in monkeys have been poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate subject performances, how these two physiological needs are satisfied in captive monkeys remains unclear. Here, we measured blood ghrelin levels and osmolality for hunger and thirst, respectively, in four captive macaques. Using enzyme-linked immunosorbent assay, we found that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (with ad libitum water), which is a typical controlled food access condition. One hour after consuming the regular dry meal, the value decreased in three out of four monkeys to within the range of individual blood ghrelin levels. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming regular dry meals with no water access. Thus, ghrelin and osmolality may provide a precise reflection of the physiological states of individual monkeys for hunger and thirst, suggesting that these indices can be used as a tool for monitoring hunger and thirst levels that mediate the animals decision-making for consuming rewards.

neuroscience↗

bioRxiv2021

Inhibition of immunoglobulin class-switching prevents pemphigus onset in desmoglein 3-specific B cell receptor knock-in mouse

Although immunoglobulin class-switching is essential for humoral immunity, its role in B-cell immune tolerance remains unclear. Pemphigus vulgaris is an autoimmune blistering disease caused by IgG targeting desmoglein 3, an adhesion molecule of keratinocytes. In this study, we generated knock-in mice that express anti-Dsg3 AK23 autoantibodies. Knock-in B cells developed normally in vivo and showed Ca2+ influx upon IgM cross-linking in vitro. The mice predominantly produced circulating AK23 IgM but little IgG antibodies. Although no IgG deposition or blister formation was observed in Dsg3-bearing tissues, Dsg3 immunization forced to induce pemphigus phenotype after class-switching to IgG in vivo. Transcriptomic analysis revealed that FCGR2B and Fc{gamma}RIIB-related genes were downregulated in B cells from peripheral blood of pemphigus patients. Indeed, in AK23 knock-in mice, Fcgr2b deficiency or haploinsufficiency spontaneously led to class-switching, AK23 IgG production, and pemphigus phenotype development. Thus, inhibition of pathogenic class-switching is a crucial tolerogenic process to prevent pemphigus onset, where attenuated Fc{gamma}RIIB signaling is one of the key predispositions to break this tolerogenic state.

immunology↗