| Summary: | 碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 98 === Stress, one of major causes of depression, can induce depressive behavior, cytokines, and stress hormone changes. Inflammatory cytokines are elevated in depressed patients and stressed animals. Systemic inflammation and stress have a synergistic effect on the levels of cytokines. The behavior tests in previous studies using LPS plus stress are too close to the LPS injections. Therefore, depression-like behavior can not be differentiated from weakness/sickness behavior.
To differentiate these two behaviors, we have designed a double-stress paradigm with sub-chronic inflammation plus inescapable foot shock by two sequential LPS injection. There are four experimental groups including control, foot shock alone, LPS alone, and double stressed groups. The behavior tests were performed 4 days afterward. Whether the LPS-induced inflammation and foot shock act synergistically on developing depression-like behaviors were examined by the escape test and forced swimming test (FST). The levels of stress-related proteins including corticosterone, brain-derived neurotrophic factor (BDNF), and S100 were evaluated by ELISA. The number of microglia was determined by florescent immunohistochemistry. The duration and failure times of the escape test was significantly increased in the double-stressed group. Mobility of the double-stressed mice is higher in the forced swimming test. There was no significant difference in locomotor activity among different groups; therefore, the depression-like behavior of the double stressed group was not due to sickness induced by LPS. The level of S100B in prefrontal cortex, BDNF in hippocampus, and corticosterone in serum was significantly increased in the double-stressed group. The number of microglia in the hippocampus of the LPS group is higher than that of the double-stressed group, which suggested that foot shock may counteract LPS effect on the activity of microglia.
IV
Our data indicated that sub-chronic inflammation plus foot shock synergistically induced depression-like behaviors and stress-related proteins in a brain regional-specific manner.
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