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24-hour-restraint stress induces long-term depressive-like phenotypes in mice

View Article: PubMed Central - PubMed

ABSTRACT

There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders.

No MeSH data available.


The 24-hour-restraint stress induced depressive-like behaviors.(A) Experiment designs to test the short-term (S group) and long-term (L group) impact of the restraint on mice. (B–C) Sucrose preference percentage of 24 hours in sucrose preference test of S group (B) and L group (C). The p-value (t-test) for S group is <0.05 (N = 24 vs. 25) and L group is <0.05 (N = 23 vs. 25). (D–E) The struggling time before the first abandon and total time of immobility in the forced swimming test of S group (D) and L group (E). The p-values of t-test of first abandon are <0.05 (N = 24 vs. N = 25) and <0.01(N = 25 vs. 28) respectively. And the p-values of t-test of immobility are <0.01 (N = 24 vs. N = 25) and <0.01 (N = 26 vs. 28) respectively. (F,G) The percentage of freezing time in the contextual fear conditioning test for the S group (F) and L group (G). The p-values of t-test are 0.30 (N = 21 vs. 23) and <0.001 (N = 20 vs. 21) respectively. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001.
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f1: The 24-hour-restraint stress induced depressive-like behaviors.(A) Experiment designs to test the short-term (S group) and long-term (L group) impact of the restraint on mice. (B–C) Sucrose preference percentage of 24 hours in sucrose preference test of S group (B) and L group (C). The p-value (t-test) for S group is <0.05 (N = 24 vs. 25) and L group is <0.05 (N = 23 vs. 25). (D–E) The struggling time before the first abandon and total time of immobility in the forced swimming test of S group (D) and L group (E). The p-values of t-test of first abandon are <0.05 (N = 24 vs. N = 25) and <0.01(N = 25 vs. 28) respectively. And the p-values of t-test of immobility are <0.01 (N = 24 vs. N = 25) and <0.01 (N = 26 vs. 28) respectively. (F,G) The percentage of freezing time in the contextual fear conditioning test for the S group (F) and L group (G). The p-values of t-test are 0.30 (N = 21 vs. 23) and <0.001 (N = 20 vs. 21) respectively. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: In order to distinguish the short-term and long-term effects of the restraint on animals’ behaviors, we separated mice into two groups (S group and L group) (Fig. 1A). Behavioral tests on S group were carried out at 2 days after the restraint, while behavioral tests on L group were performed at 35 days after the restraint. Before the 24-hour-restraint, we conducted sucrose preference test to measure the level of experiencing pleasure. As a result, there’s no difference of sucrose preference between the unrestraint mice and the control before the 24-hour-restraint (Supplementary Figures S4 and S5). However, after the restraint, mice displayed a decreased sucrose preference than the controls in both S group and L group (Fig. 1B,C). These results suggested the restraint mice lack reactivity to pleasure, known as anhedonia, which is a core symptom of depression20. In the forced swimming test, a measure of behavioral despair, reduced latency to abandon and increased immobility were found in the restraint mice for both S group (Fig. 1D) and L group (Fig. 1E). Moreover, we carried out the contextual fear-conditioning (CFC) test to assess the fear memory. There was no difference in freezing time between the restraint and the control mice in S group (Fig. 1F). Interestingly, the restraint mice exhibited less freezing time in L group (Fig. 1G). Previous study also reported that animals exposed to chronic stress showed deficits in learning and cognition flexibility21. The CFC tests indicated that the 24-hour restraint could induce abnormal cognition function and the visible abnormality occurred after long-time accumulation.


24-hour-restraint stress induces long-term depressive-like phenotypes in mice
The 24-hour-restraint stress induced depressive-like behaviors.(A) Experiment designs to test the short-term (S group) and long-term (L group) impact of the restraint on mice. (B–C) Sucrose preference percentage of 24 hours in sucrose preference test of S group (B) and L group (C). The p-value (t-test) for S group is <0.05 (N = 24 vs. 25) and L group is <0.05 (N = 23 vs. 25). (D–E) The struggling time before the first abandon and total time of immobility in the forced swimming test of S group (D) and L group (E). The p-values of t-test of first abandon are <0.05 (N = 24 vs. N = 25) and <0.01(N = 25 vs. 28) respectively. And the p-values of t-test of immobility are <0.01 (N = 24 vs. N = 25) and <0.01 (N = 26 vs. 28) respectively. (F,G) The percentage of freezing time in the contextual fear conditioning test for the S group (F) and L group (G). The p-values of t-test are 0.30 (N = 21 vs. 23) and <0.001 (N = 20 vs. 21) respectively. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5016966&req=5

f1: The 24-hour-restraint stress induced depressive-like behaviors.(A) Experiment designs to test the short-term (S group) and long-term (L group) impact of the restraint on mice. (B–C) Sucrose preference percentage of 24 hours in sucrose preference test of S group (B) and L group (C). The p-value (t-test) for S group is <0.05 (N = 24 vs. 25) and L group is <0.05 (N = 23 vs. 25). (D–E) The struggling time before the first abandon and total time of immobility in the forced swimming test of S group (D) and L group (E). The p-values of t-test of first abandon are <0.05 (N = 24 vs. N = 25) and <0.01(N = 25 vs. 28) respectively. And the p-values of t-test of immobility are <0.01 (N = 24 vs. N = 25) and <0.01 (N = 26 vs. 28) respectively. (F,G) The percentage of freezing time in the contextual fear conditioning test for the S group (F) and L group (G). The p-values of t-test are 0.30 (N = 21 vs. 23) and <0.001 (N = 20 vs. 21) respectively. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: In order to distinguish the short-term and long-term effects of the restraint on animals’ behaviors, we separated mice into two groups (S group and L group) (Fig. 1A). Behavioral tests on S group were carried out at 2 days after the restraint, while behavioral tests on L group were performed at 35 days after the restraint. Before the 24-hour-restraint, we conducted sucrose preference test to measure the level of experiencing pleasure. As a result, there’s no difference of sucrose preference between the unrestraint mice and the control before the 24-hour-restraint (Supplementary Figures S4 and S5). However, after the restraint, mice displayed a decreased sucrose preference than the controls in both S group and L group (Fig. 1B,C). These results suggested the restraint mice lack reactivity to pleasure, known as anhedonia, which is a core symptom of depression20. In the forced swimming test, a measure of behavioral despair, reduced latency to abandon and increased immobility were found in the restraint mice for both S group (Fig. 1D) and L group (Fig. 1E). Moreover, we carried out the contextual fear-conditioning (CFC) test to assess the fear memory. There was no difference in freezing time between the restraint and the control mice in S group (Fig. 1F). Interestingly, the restraint mice exhibited less freezing time in L group (Fig. 1G). Previous study also reported that animals exposed to chronic stress showed deficits in learning and cognition flexibility21. The CFC tests indicated that the 24-hour restraint could induce abnormal cognition function and the visible abnormality occurred after long-time accumulation.

View Article: PubMed Central - PubMed

ABSTRACT

There is an increasing risk of mental disorders, such as acute stress disorder (ASD), post-traumatic stress disorder (PTSD) and depression among survivors who were trapped in rubble during earthquake. Such long-term impaction of a single acute restraint stress has not been extensively explored. In this study, we subjected mice to 24-hour-restraint to simulate the trapping episode, and investigated the acute (2 days after the restraint) and long-term (35 days after the restraint) impacts. Surprisingly, we found that the mice displayed depression-like behaviors, decreased glucose uptake in brain and reduced adult hippocampal neurogenesis 35 days after the restraint. Differential expression profiling based on microarrays suggested that genes and pathways related to depression and other mental disorders were differentially expressed in both PFC and hippocampus. Furthermore, the depression-like phenotypes induced by 24-hour-restraint could be reversed by fluoxetine, a type of antidepressant drug. These findings demonstrated that a single severe stressful event could produce long-term depressive-like phenotypes. Moreover, the 24-hour-restraint stress mice could also be used for further studies on mood disorders.

No MeSH data available.