Dataset Information

Altered behavior in mice with deletion of the alpha2-antiplasmin gene.

ABSTRACT:

Background

The ?2-antiplasmin (?2AP) protein is known to be a principal physiological inhibitor of plasmin, and is expressed in various part of the brain, including the hippocampus, cortex, hypothalamus and cerebellum, thus suggesting a potential role for ?2AP in brain functions. However, the involvement of ?2AP in brain functions is currently unclear.

Objectives

The goal of this study was to investigate the effects of the deletion of the ?2AP gene on the behavior of mice.

Methods

The motor function was examined by the wire hang test and rotarod test. To evaluate the cognitive function, a repeated rotarod test, Y-maze test, Morris water maze test, passive or shuttle avoidance test and fear conditioning test were performed. An open field test, dark/light transition test or tail suspension test was performed to determine the involvement of ?2AP in anxiety or depression-like behavior.

Results and conclusions

The ?2AP knockout (?2AP-/-) mice exhibited impaired motor function compared with ?2AP+/+ mice. The ?2AP-/- mice also exhibited impairments in motor learning, working memory, spatial memory and fear conditioning memory. Furthermore, the deletion of ?2AP induced anxiety-like behavior, and caused an anti-depression-like effect in tail suspension. Therefore, our findings suggest that ?2AP is a crucial mediator of motor function, cognitive function, anxiety-like behavior and depression-like behavior, providing new insights into the role of ?2AP in the brain functions.

SUBMITTER: Kawashita E

PROVIDER: S-EPMC4038522 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Altered behavior in mice with deletion of the alpha2-antiplasmin gene.

Kawashita Eri E Kanno Yosuke Y Ikeda Kanako K Kuretake Hiromi H Matsuo Osamu O Matsuno Hiroyuki H

PloS one 20140529 5

<h4>Background</h4>The α2-antiplasmin (α2AP) protein is known to be a principal physiological inhibitor of plasmin, and is expressed in various part of the brain, including the hippocampus, cortex, hypothalamus and cerebellum, thus suggesting a potential role for α2AP in brain functions. However, the involvement of α2AP in brain functions is currently unclear.<h4>Objectives</h4>The goal of this study was to investigate the effects of the deletion of the α2AP gene on the behavior of mice.<h4>Meth ...[more]

PMID: 24874880

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Project description: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.

Dataset Information

Altered behavior in mice with deletion of the alpha2-antiplasmin gene.

Background

Objectives

Methods

Results and conclusions

Publications

Altered behavior in mice with deletion of the alpha2-antiplasmin gene.

Similar Datasets

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