Altered behavior in mice overexpressing soluble ST2

Abstract

Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior.

IL-33 in Mental Disorders

“…As noted above, sST2 is the soluble receptor of IL-33, and it is a key molecule for the immune system too. One researcher revealed that sST2 overexpression in mice resulted in decreased social interaction [ 42 ].…”

Plasma soluble suppression of tumorigenicity 2 and depression after acute ischemic stroke

“…Limited studies have reported the association between sST2 and depression. Kikuchi and colleagues established an animal model, and found that sST2 overexpression may reduce social behavior and enhance depressive‐like behavior by changing the composition of gut microbiota [34]. Another study conducted in 349 type 2 diabetes mellitus (T2DM) and non‐T2DM men with asymptomatic stage B heart failure (HF) indicated that T2DM HF patients had higher circulating levels of sST2 and had more somatic/affective depressive symptoms [14].…”

Desflurane and Sevoflurane Induce Prolonged Motor Learning Deficits in aged AppNL-G-F/ NL-G-F Mice.

“…1. Before beginning testing, each mouse was observed in a clean cage for a general health check and neurological screening tests according to methods of our previous reports [28,[38][39][40]. The neurological screening tests were designed to detect any gross abnormalities in physical function.…”