Aims
Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant‐like effects in male rodents. However, depression ...is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant‐like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)‐induced depression.
Methods
Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety‐ and depression‐like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element‐binding protein (p‐CREB) and brain‐derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants.
Results
Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p‐CREB and BDNF in the hippocampus.
Conclusion
OT may exert antidepressant‐like effects by activating hippocampal CREB‐BDNF signaling in a female mouse model of depression.
Psychosocial stress factors, such as threat and defeat, are major risk factors for the development of depression. The precise mechanisms underlying stress-induced depression are not clearly ...understood because the stress response in the brain varies in a stress-frequency-dependent manner. In the current research milieu on the pathogenesis of depression, the focus is on depression-like behavioral phenotype, hypothalamic-pituitary-adrenal (HPA) axis, and hippocampal neurogenesis. However, most studies have evaluated the symptomatic features of depression at certain time points after exposure to psychosocial stress. Here, we examined the frequency-dependent effects of psychosocial stress on depression-related features in rats.
In the present study, different frequencies (one, two, three, or four times) of psychosocial stress were applied to 19 male Sprague-Dawley rats using a resident/intruder paradigm. Subsequently, the rats were subjected to a stress reactivity test to evaluate HPA axis activity, following which assessments of immobility behavior in the forced swimming test (FST) and adult neurogenesis were conducted.
One-time stressed rats showed a decrease in immobility behavior in the FST and the amount of doublecortin (DCX)-positive cells. Two-time stress caused hypoactivity of the HPA axis. In contrast, immobility behavior and HPA axis activity were increased after four-time stress exposure, but the number of DCX-positive cells was decreased.
Our findings suggest that psychosocial stress produces a biphasic effect on the symptoms of depression in a stress-frequency-dependent manner, which could provide insights to facilitate further pathogenesis research on depression.
Chronic psychosocial stress stands as a significant heterogeneous risk factor for psychiatric disorders. The brain’s physiological response to such stress varies based on the frequency and intensity ...of stress episodes. However, whether stress episodes divergently could affect hippocampal cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling remains unclear, a key regulator of psychiatric symptoms. We aimed to assess how two distinct patterns of social defeat stress exposure impact anxiety- and depression-like behaviors, fear, and hippocampal CREB-BDNF signaling in adult male rats. To explore this, adult male Sprague-Dawley rats were subjected to psychosocial stress using a Resident/Intruder paradigm for ten consecutive days (continuous social defeat stress: CS) or ten social defeat stress over the course of 21 days (intermittent social defeat stress IS). Behavioral tests (including novelty-suppressed feeding test, forced swimming test, and contextually conditioned fear) were conducted. Protein expression levels of phosphorylated CREB and BDNF in the dorsal and ventral hippocampi were examined. CS led to heightened anxiety-like behavior, fear, and increased levels of phosphorylated CREB in both the dorsal and ventral hippocampi. Conversely, IS resulted in increased anxiety-like behavior and behavioral despair alongside decreased levels of phosphorylated CREB and BDNF, particularly in the dorsal hippocampus. These findings indicate that chronic psychosocial stress divergently affects hippocampal CREB-BDNF signaling and emotional regulation depending on the stress episode. Such insights could enhance our understanding of the molecular basis of the heterogeneity of psychiatric disorders and facilitate the development of innovative treatment approaches to patients with psychiatric disorders.
•Male rats were subjected to post-weaning social isolation for 9 weeks.•Social isolation induced cognitive dysfunction, anxiety, and aggression.•Social isolation increased the levels of α1 adrenergic ...receptor protein in the mPFC.
Early-life social isolation induces emotional and cognitive dysregulation, such as increased aggression and anxiety, and decreases neuron excitability in the medial prefrontal cortex (mPFC). The noradrenergic system in the mPFC regulates emotion and cognitive function via α1 or α2A adrenergic receptors, depending on noradrenaline levels. However, social isolation-induced changes in the mPFC noradrenergic system have not been reported. Here, male Wistar rats received post-weaning social isolation for nine consecutive weeks and were administered behavioral tests (novel object recognition, elevated plus maze, aggression, and forced swimming, sequentially). Protein expression levels in the mPFC noradrenergic system (α1 and α2A adrenergic receptors, tyrosine hydroxylase, and dopamine-β-hydroxylase used as indices of noradrenaline synthesis and release) were examined through western blotting. Social isolation caused cognitive dysfunction, anxiety-like behavior, and aggression, but not behavioral despair. Socially-isolated rats exhibited increased protein levels of the α1 adrenergic receptor, tyrosine hydroxylase, and dopamine-β-hydroxylase in the mPFC; there was no significant difference between the groups in the α2A adrenergic receptor expression levels. Preferential activation of the α1 adrenergic receptor caused by high noradrenaline concentration in the mPFC may be involved in social isolation-induced emotional and cognitive regulation impairments. Targeting the α1 adrenergic receptor signaling pathway is a potential therapeutic strategy for psychiatric disorders with symptomatic features such as emotional and cognitive dysregulation.
•Rats were exposed to social defeat stress exposure for 10 consecutive days.•Social defeat stress induced anxiety-like behavior, but not depressive-like behaviors.•Continuous psychosocial stress ...increased the cell proliferation in the dorsal hippocampus.•Continuous psychosocial stress decreased the immature newborn neurons in the dorsal hippocampus.•Social defeat stress increased BMP signaling in the dorsal hippocampus.
Bone morphogenetic protein (BMP) signaling in the hippocampus regulates psychiatric behaviors and hippocampal neurogenesis in non-stress conditions; however, stress-induced changes in hippocampal BMP signaling have not yet been reported. Therefore, we sought to examine whether psychosocial stress, which induces psychiatric symptoms, affects hippocampal BMP signaling. A total of 32 male Sprague-Dawley rats were exposed to a psychosocial stress using a Resident/Intruder paradigm for ten consecutive days. Subsequently, rats were subjected to a battery of behavioral tests (novelty-suppressed feeding test, sucrose preference test, and forced swimming test) for the evaluation of adult neurogenesis and activity of BMP signaling in the dorsal and ventral hippocampus. Repeated social defeat promoted anxiety-like behaviors, but neither anhedonia nor behavioral despair. Socially defeated rats exhibited an increase in the number of Ki-67-positive cells, decrease in the number of doublecortin (DCX)-positive cells, and decrease only in the dorsal hippocampus of the ratio of DCX-positive to Ki-67-positive cells, a proxy for newly-born cell maturation speed and survival. In contrast, no differences were observed in the number of 5-Bromo-2′-deoxyuridine (BrdU)-positive cells, indicating survival of newly-born cells both in the dorsal and ventral hippocampus. Furthermore, psychosocial stress significantly increased the BMP-4 and phosphorylated Smad1/5/9 expression levels specifically in the dorsal hippocampus. Our findings suggest that repeated psychosocial stress activates BMP signaling and differently affects cell proliferation and neurogenesis exclusively in the dorsal hippocampus, potentially exacerbating anxiety-related symptoms. Targeting BMP signaling is a potential therapeutic strategy for psychiatric disorders.
Early-life social isolation induces emotional and cognitive dysregulation, such as increased aggression and anxiety, and decreases neuron excitability in the medial prefrontal cortex (mPFC). The ...noradrenergic system in the mPFC regulates emotion and cognitive function via α
or α
adrenergic receptors, depending on noradrenaline levels. However, social isolation-induced changes in the mPFC noradrenergic system have not been reported. Here, male Wistar rats received post-weaning social isolation for nine consecutive weeks and were administered behavioral tests (novel object recognition, elevated plus maze, aggression, and forced swimming, sequentially). Protein expression levels in the mPFC noradrenergic system (α
and α
adrenergic receptors, tyrosine hydroxylase, and dopamine-β-hydroxylase used as indices of noradrenaline synthesis and release) were examined through western blotting. Social isolation caused cognitive dysfunction, anxiety-like behavior, and aggression, but not behavioral despair. Socially-isolated rats exhibited increased protein levels of the α
adrenergic receptor, tyrosine hydroxylase, and dopamine-β-hydroxylase in the mPFC; there was no significant difference between the groups in the α
adrenergic receptor expression levels. Preferential activation of the α
adrenergic receptor caused by high noradrenaline concentration in the mPFC may be involved in social isolation-induced emotional and cognitive regulation impairments. Targeting the α
adrenergic receptor signaling pathway is a potential therapeutic strategy for psychiatric disorders with symptomatic features such as emotional and cognitive dysregulation.
BackgroundDepression is twice as common in women as in men. Glucocorticoid (GC) exposure is a major risk factor for depression. Oxytocin (OT) has been shown to exert antidepressant-like effect via ...enhancement of CREB-BDNF pathway in the hippocampus, a key factor of mood regulation. However, it is remains unclear whether the hippocampal CREB-BDNF pathway is related to the antidepressant-like effect of OT under conditions of GC exposure, particularly in the dexamethasone (DEX)-induced depression model of female mice.MethodsFemale C57BL/6J mice were used in this study. All mice were administered with either saline (vehicle), DEX (5 mg/kg), or OT (1 mg/kg) + DEX (5 mg/kg) for eight weeks. After the termination of drug administration, animals were assessed of depression-like behavior by forced swimming test (FST). The day after the FST, the mice were sacrificed under anesthesia and their hippocampus were evaluated for phosphorylated CREB (p-CREB) and BDNF protein levels by western blot analyses.ResultsOT+DEX mice showed a significantly lower immobility time compared to the DEX mice in the FST. The immobility time of OT+DEX group was comparable with the vehicle group. In the hippocampus, BDNF and p-CREB protein levels were significantly higher in the OT+DEX group than in the vehicle and DEX groups.DiscussionSimultaneous OT treatment blocked the adverse effects of DEX. OT treatment upregulated p-CREB and BDNF levels of the DEX exposed hippocampus. These results suggest OT exerts its antidepressant-like effect by activating the hippocampal CREB-BDNF signaling pathway in female.
The present study aimed to assess if there is a gender difference in thermal perception, and estrogen is involved in the mechanism. MethodsMale (M group) and female ICR mice were used (n=6 and 18, ...respectively). Each mouse was placed a device for temperature measurement in the abdominal cavity under general anesthesia. Female mice were divided to three groups: two groups were bilaterally ovariectomized with and without estradiol replacement (E2 and N groups) and one sham‐operated (F group). Mice were placed in an experiment box (50x12x15 cm), of which 5 Pertier boards at the bottom. Each board temperature was controlled by computer program, and changed each 6 min for 90 min. The temperature was selected from either of 28°C, 31°C, 34°C, 37°C, and 40°C with a difference from that of the other boards. Abdominal temperature (Tabd) and the position of a mouse and its board temperature were recorded every 1 min. Experiment was started after 60‐min baseline period with all boards set at 34°C. Mice were habituated to the box 2‐3 times before the experiment. ResultsDuring the housing period before the experiment, there were no differences in Tabd among the groups; however, during the experiment, Tabd was higher in the F group than in the M group. In addition, the F group preferred 40°C board, but the M group 34°C board. There were no differences in Tabd and temperature preference of the board among the F, E2 and N groups. Conclusion In this experimental condition, male mice showed higher environmental condition than female mice. However, estradiol is not likely mechanism for the difference.
Grant Funding Source: MEXT.KIBANKEISEI
BackgroundDepression is twice as common in women as in men. Glucocorticoid (GC) exposure is a major risk factor for depression. Oxytocin (OT) has been shown to exert antidepressant-like effect via ...enhancement of CREB-BDNF pathway in the hippocampus, a key factor of mood regulation. However, it is remains unclear whether the hippocampal CREB-BDNF pathway is related to the antidepressant-like effect of OT under conditions of GC exposure, particularly in the dexamethasone (DEX)-induced depression model of female mice.MethodsFemale C57BL/6J mice were used in this study. All mice were administered with either saline (vehicle), DEX (5 mg/kg), or OT (1 mg/kg) + DEX (5 mg/kg) for eight weeks. After the termination of drug administration, animals were assessed of depression-like behavior by forced swimming test (FST). The day after the FST, the mice were sacrificed under anesthesia and their hippocampus were evaluated for phosphorylated CREB (p-CREB) and BDNF protein levels by western blot analyses.ResultsOT+DEX mice showed a significantly lower immobility time compared to the DEX mice in the FST. The immobility time of OT+DEX group was comparable with the vehicle group. In the hippocampus, BDNF and p-CREB protein levels were significantly higher in the OT+DEX group than in the vehicle and DEX groups.DiscussionSimultaneous OT treatment blocked the adverse effects of DEX. OT treatment upregulated p-CREB and BDNF levels of the DEX exposed hippocampus. These results suggest OT exerts its antidepressant-like effect by activating the hippocampal CREB-BDNF signaling pathway in female.
[Demo paper] twitter visual event mining system Kaneko, Takamu; Harada, Hiroyoshi; Yanai, Keiji
2013 IEEE International Conference on Multimedia and Expo Workshops (ICMEW),
2013-July
Conference Proceeding
In this demo, we demonstrate a system to mine events visually from the Twitter stream by making use of "geo-tweet photos". Some works on event mining which utilize geotagged tweets have been proposed ...so far. However, they used no images but only textual analysis of tweet texts. In this work, we detect events using visual information as well as textual information, which is the first work to mine event photos automatically from a huge number of Twitter photos, as long as we know. In the experiments, we show some examples of detected events and their photos such as "blooming cherry blossom" and "Tokyo firefly festival".
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