Limits...
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.


Related in: MedlinePlus

Alternations of glucose metabolism by small animal PET scanning.Glucose uptake is measured as %ID/cc (%injected dose per mL of tissue). (A) Experiment design of the PET scanning. (B) The average glucose uptake of the whole brain of S group shows no difference between control and restraint mice (N = 7 vs. 9). (C) The changes of glucose uptake in brain regions of S group. Glucose uptake of brain regions including STR, CTX, BFS, LAMY, SC, OLF, RIC is significantly increased in restraint mice. (D) The average glucose uptake of the whole brain for L group is significantly decreased in restraint mice (N = 8 vs. N = 7), p value of student t-test is<0.01. (E) The glucose uptake of different brain regions of L group. Brain regions such as STR, CTX, HIP, THA, CG, SC, MID and IC were significantly decreased in restraint mice. (F) Representatives of the glucose uptake of S and L group. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01. Abbreviations: RSTR, right striatum; LSTR, left striatum; CTX, cortex; RHIP, right hippocampal region; LHIP, left hippocampal region; THA, thalamus; CB, cerebellum; BFS, basal forebrain/septum; HYP, hypothalamus; RAMY, right amygdala; LAMY, left amygdala; CG, cingulate gyrus; SC, superior colliculus; OLF, olfactory areas; RMID, right midbrain; LMID, left midbrain; LIC, left inferior colliculus; RIC, right inferior colliculus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5016966&req=5

f2: Alternations of glucose metabolism by small animal PET scanning.Glucose uptake is measured as %ID/cc (%injected dose per mL of tissue). (A) Experiment design of the PET scanning. (B) The average glucose uptake of the whole brain of S group shows no difference between control and restraint mice (N = 7 vs. 9). (C) The changes of glucose uptake in brain regions of S group. Glucose uptake of brain regions including STR, CTX, BFS, LAMY, SC, OLF, RIC is significantly increased in restraint mice. (D) The average glucose uptake of the whole brain for L group is significantly decreased in restraint mice (N = 8 vs. N = 7), p value of student t-test is<0.01. (E) The glucose uptake of different brain regions of L group. Brain regions such as STR, CTX, HIP, THA, CG, SC, MID and IC were significantly decreased in restraint mice. (F) Representatives of the glucose uptake of S and L group. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01. Abbreviations: RSTR, right striatum; LSTR, left striatum; CTX, cortex; RHIP, right hippocampal region; LHIP, left hippocampal region; THA, thalamus; CB, cerebellum; BFS, basal forebrain/septum; HYP, hypothalamus; RAMY, right amygdala; LAMY, left amygdala; CG, cingulate gyrus; SC, superior colliculus; OLF, olfactory areas; RMID, right midbrain; LMID, left midbrain; LIC, left inferior colliculus; RIC, right inferior colliculus.

Mentions: Neurons account for the majority energy consumption of brain, therefore the dynamic changes of energy demand reflex the alteration in neuronal activation, which can be measured by18 F-fuoro-2-deoxyglucose (FDG)-PET scanning22. Hence we checked the brain glucose metabolism by small-animal PET scanning (Fig. 2A). In S group, the glucose uptake of specific brain regions were increased in restraint mice, including striatum (STR), cortex (CTX), basal forebrain/septum (BS), left amygdala (LAMY), superior colliculus (SC), olfactory areas (OLF) and right inferior colliculus (RIC) (Fig. 2C). However the average glucose uptake of the whole brain showed no significant difference (Fig. 3B). While in L group, it was significantly decreased in the restraint mice (Fig. 2D). The brain regions with decreased glucose uptake consist of STR, CTX, SC and IC, which were increased in the S group. In addition, brain regions including hippocampal region (HIP), thalamus (THA), cingulate gyrus (CG) and midbrain (MID) were also found to display decreased glucose uptake in L group (Fig. 2E). Our results showed that 24-hour-restraint could alter the glucose uptake of brain, differently in short term and long term.


24-hour-restraint stress induces long-term depressive-like phenotypes in mice
Alternations of glucose metabolism by small animal PET scanning.Glucose uptake is measured as %ID/cc (%injected dose per mL of tissue). (A) Experiment design of the PET scanning. (B) The average glucose uptake of the whole brain of S group shows no difference between control and restraint mice (N = 7 vs. 9). (C) The changes of glucose uptake in brain regions of S group. Glucose uptake of brain regions including STR, CTX, BFS, LAMY, SC, OLF, RIC is significantly increased in restraint mice. (D) The average glucose uptake of the whole brain for L group is significantly decreased in restraint mice (N = 8 vs. N = 7), p value of student t-test is<0.01. (E) The glucose uptake of different brain regions of L group. Brain regions such as STR, CTX, HIP, THA, CG, SC, MID and IC were significantly decreased in restraint mice. (F) Representatives of the glucose uptake of S and L group. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01. Abbreviations: RSTR, right striatum; LSTR, left striatum; CTX, cortex; RHIP, right hippocampal region; LHIP, left hippocampal region; THA, thalamus; CB, cerebellum; BFS, basal forebrain/septum; HYP, hypothalamus; RAMY, right amygdala; LAMY, left amygdala; CG, cingulate gyrus; SC, superior colliculus; OLF, olfactory areas; RMID, right midbrain; LMID, left midbrain; LIC, left inferior colliculus; RIC, right inferior colliculus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Alternations of glucose metabolism by small animal PET scanning.Glucose uptake is measured as %ID/cc (%injected dose per mL of tissue). (A) Experiment design of the PET scanning. (B) The average glucose uptake of the whole brain of S group shows no difference between control and restraint mice (N = 7 vs. 9). (C) The changes of glucose uptake in brain regions of S group. Glucose uptake of brain regions including STR, CTX, BFS, LAMY, SC, OLF, RIC is significantly increased in restraint mice. (D) The average glucose uptake of the whole brain for L group is significantly decreased in restraint mice (N = 8 vs. N = 7), p value of student t-test is<0.01. (E) The glucose uptake of different brain regions of L group. Brain regions such as STR, CTX, HIP, THA, CG, SC, MID and IC were significantly decreased in restraint mice. (F) Representatives of the glucose uptake of S and L group. Data are presented as mean ± SEM, *P < 0.05, **P < 0.01. Abbreviations: RSTR, right striatum; LSTR, left striatum; CTX, cortex; RHIP, right hippocampal region; LHIP, left hippocampal region; THA, thalamus; CB, cerebellum; BFS, basal forebrain/septum; HYP, hypothalamus; RAMY, right amygdala; LAMY, left amygdala; CG, cingulate gyrus; SC, superior colliculus; OLF, olfactory areas; RMID, right midbrain; LMID, left midbrain; LIC, left inferior colliculus; RIC, right inferior colliculus.
Mentions: Neurons account for the majority energy consumption of brain, therefore the dynamic changes of energy demand reflex the alteration in neuronal activation, which can be measured by18 F-fuoro-2-deoxyglucose (FDG)-PET scanning22. Hence we checked the brain glucose metabolism by small-animal PET scanning (Fig. 2A). In S group, the glucose uptake of specific brain regions were increased in restraint mice, including striatum (STR), cortex (CTX), basal forebrain/septum (BS), left amygdala (LAMY), superior colliculus (SC), olfactory areas (OLF) and right inferior colliculus (RIC) (Fig. 2C). However the average glucose uptake of the whole brain showed no significant difference (Fig. 3B). While in L group, it was significantly decreased in the restraint mice (Fig. 2D). The brain regions with decreased glucose uptake consist of STR, CTX, SC and IC, which were increased in the S group. In addition, brain regions including hippocampal region (HIP), thalamus (THA), cingulate gyrus (CG) and midbrain (MID) were also found to display decreased glucose uptake in L group (Fig. 2E). Our results showed that 24-hour-restraint could alter the glucose uptake of brain, differently in short term and long term.

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.


Related in: MedlinePlus