Susceptibility to chronic immobilization stress-induced depressive-like behaviour in middle-aged female mice and accompanying changes in dopamine D1 and GABAA receptors in related brain regions.

BACKGROUND: Middle-aged females, especially perimenopausal females, are vulnerable to depression, but the potential mechanism remains unclear. Dopaminergic and GABAergic system dysfunction is involved in the pathophysiology of depression. In the current study, we used 2-month-old and 11-month-old C57BL/6 mice as young and middle-aged mice, respectively. Chronic immobilization stress (CIS) was used to induce depressive-like behaviour, and the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess these behaviours. We then measured the mRNA levels of dopamine receptor D1 (DRD1) and the GABAA receptors GABRA1, GABRB2 and GABRG2 in the nucleus accumbens (NAc) and prefrontal cortex (PFC). RESULTS: We found that immobility time in the FST was significantly increased in the middle-aged mice compared with the middle-aged control mice and the young mice. In addition, the preference for sucrose water was reduced in the middle-aged mice compared with the middle-aged control mice. However, CIS did not induce obvious changes in the performance of the young mice in our behavioural tests. Moreover, the middle-aged mice exhibited equal immobility times as the young mice in the absence of stress. Decreases in the mRNA levels of DRD1, GABRA1, and GABRB2 but not GABRG2 were found in the NAc and PFC in the middle-aged mice in the absence of stress. Further decreases in the mRNA levels of DRD1 in the NAc and GABRG2 in the NAc and PFC were found in the middle-aged mice subjected to CIS. CONCLUSIONS: Our results suggested that ageing could not directly induce depression in the absence of stress. However, ageing could induce susceptibility to depression in middle-aged mice in the presence of stress. CIS-induced decreases in DRD1 and GABRG2 levels might be involved in the increase in susceptibility to depression in this context.

Molecular analysis of curcumin-induced polarization of murine RAW264.7 macrophages.

This study aimed to investigate the effects of curcumin on macrophages polarization and possible mechanism involved, and to analyze the molecular basis of its antiatherosclerosis activity. RAW264.7 macrophages (M0) and M1 macrophages were treated with curcumin at 0, 6.25, 12.5, and 25 µmol/L with or without GW9662. Using real-time polymerase chain reaction and Western blot analysis, we examined the phenotype markers of M1 [iNOS, interleukin (IL)-1ß, IL-6, and MCP-1] and M2 (KLF4, FIZZ1, and MGL1] macrophages. Curcumin reduced the expression of the M1 phenotype markers and upregulated the expression of proliferator-activated receptor γ in M0 and M1 macrophages and IKBα in M1 macrophages. When M1 macrophages were incubated with curcumin and GW9662, the expression of the M1 phenotype markers was decreased, while IKBα was upregulated. The expression of the M2 phenotype markers in M0 and M1 macrophages was upregulated after the curcumin treatment. When M0 and M1 macrophages were incubated with curcumin and GW9662, the expression of the M2 phenotype markers was reduced. Curcumin inhibited the M1 inflammation phenotype as a result of the direct activation of IKBα and polarized the macrophages to become M2 phenotype through the activation of proliferator-activated receptor γ. These findings provide new clues to develop new drug therapy for atherosclerosis.

Distinct roles of dopamine D3 receptors in modulating methamphetamine-induced behavioral sensitization and ultrastructural plasticity in the shell of the nucleus accumbens.

Persistent changes in behavior and psychological function that occur as a consequence of exposure to drugs of abuse are thought to be mediated by the structural plasticity of specific neural circuits such as the brain's dopamine (DA) system. Changes in dendritic morphology in the nucleus accumbens (NAc) accompany drug-induced enduring behavioral and molecular changes, yet ultrastructural changes in synapses following repeated exposure to drugs have not been well studied. The current study examines the role of DA D3 receptors in modulating locomotor activity induced by both acute and repeated methamphetamine (METH) administration and accompanying ultrastructural plasticity in the shell of NAc in mice. We found that D3 receptor mutant (D3−/−) mice exhibited attenuated acute locomotor responses as well as the development of behavioral sensitization to METH compared with wild-type mice. In the absence of obvious neurotoxic effects, METH induced similar increases in synaptic density in the shell of NAc in both wild-type and D3−/− mice. These results suggest that D3 receptors modulate locomotor responses to both acute and repeated METH treatment. In contrast, the D3 receptor is not obviously involved in modulating baseline or METH-induced ultrastructural changes in the NAc shell.

[Structural plasticity associated with drugs addiction].

An essential feature of drug addiction is that an individual continues to use drug despite the threat of severely adverse physical or psychosocial consequences. Persistent changes in behavior and psychological function that occur as a function of drugs of abuse are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits (especially the brains reward circuits). In this paper we summarized evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced persistent changes in the structure of dendrites and dendritic spines on cells in relevant brain regions. We also approached the potential molecular mechanisms of these changes. It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

Application and nursing key points of wet dressings on the intestinal stoma after enterostomy.

Patients with severe intestinal injury caused by trauma and malignant intestinal diseases require an artificial anus to be established through enterostomy to replace the original perineal anus for defecation. Although enterostomy has brought a new way of defecation to patients, the nursing requirements for an intestinal stoma after enterostomy are high. If complications arise from improper postoperative wound care, the quality of life of patients will be seriously reduced, and the psychological burden will be aggravated. This study compared the nursing effect of wet dressings and traditional dry dressings on patients undergoing enterostomy. Results showed that compared to patients using dry dressings, patients who used wet dressings had significantly lower postoperative dressing change frequency and complication rate, less pain during dressing change, and shorter hospital stays and intestinal stoma incision healing time. This suggests that wet dressings can promote wound healing in patients with enterostomy. In addition, it was found that compared to patients using dry dressings, the postoperative sleep quality, mood score, and quality of life of patients using wet dressings were significantly better. Evaluation of patient care comfort and satisfaction revealed that patients who used wet dressings felt significantly more comfortable and satisfied with their care than those who used dry dressings. Therefore, this study argues that wet dressings can facilitate the wound healing of the intestinal stoma in patients with enterostomy more than dry dressings, and better alleviate the bad moods and improve the quality of life of patients. Wet dressing can be used as a preferred nursing method for patients undergoing enterostomy.

Effect of combined intravenous-inhalation anesthesia on postoperative cognitive dysfunction after laparoscopic radical resection of cervical cancer: A protocol for systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of combined intravenous-inhalation anesthesia (CIVIA) on postoperative cognitive dysfunction (POCD) after laparoscopic radical resection of cervical cancer. METHODS: By using a predefined standardized study protocol, we conducted a systematic review of randomized controlled trials (RCTs) with meta-analysis, searching the following data bases: PubMed, Embase, Web of Science, and Cochrane Library. RESULTS: This systematic review evaluated the effect of CIVIA on POCD after laparoscopic radical resection of cervical cancer. CONCLUSION: This systematic review provided up-to-date evidence to evaluate the effect of CIVIA on POCD after laparoscopic radical resection of cervical cancer. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/82FNA.

Decreased expression of CD200 and CD200R1 by human decidual tissues in spontaneous early abortion.

Objective: To examine the cellular distribution and the expression of CD200 and its receptor 1 (CD200R1) in human deciduas in first-trimester pregnant women with spontaneous early abortion (SEA) and normal pregnancy, and to explore their role in the etiology of SEA.Subjects and methods: Thirty-five women at 6-10-week gestation with SA and 30 women of similar gestational age with a healthy pregnancy were recruited. Expression of CD200 and CD200R1 in the deciduas was determined using immunohistochemistry, confocal laser scanning microscope, Western blot, and real-time PCR (RT-PCR).Results: The decidual stromal cells, glandular epithelial cells, and vessel endothelial cells during the first trimester of pregnancy express both CD200 and CD200R1 proteins. During this period, the expression of CD200 in glandular epithelial cells and vessel endothelial cells is significantly higher in normal pregnancy than that in women with SEA (0.3079 ± 0.0674 versus 0.2735 ± 0.0515; 0.4077 ± 0.1366 versus 0.3249 ± 0.0993); the expression of CD200R1 in stromal cells, decidual stromal cells, glandular epithelial cells is significantly higher during normal pregnancy than SEA (0.2574 ± 0.0588 versus 0.2292 ± 0.0415; 0.3617 ± 0.1046 versus 0.2804 ± 0.0640). Western blot analysis showed an approximately 44% decrease in CD200R1expression in decidua in the SEA versus the controls. Finally, in decidua, the expression of both CD200 protein and CD200R1 transcript are significantly higher in healthy first-trimester pregnancy than in SEA (CD200: 2.2089 ± 1.2754 versus 0.7241 ± 0.2143; CD200R1: 15.7843 ± 10.7085 versus 7.3381 ± 5.8529).Conclusions: Women with SEA have a lower level of CD200 and CD200R1 expression in deciduas compared with normal pregnant women suggesting that under physiological conditions, CD200 and CD200R1 expression by deciduas is important to prevent fetal loss ensure a successful pregnancy.

The inhibitory effect of levo-tetrahydropalmatine on the methamphetamine-induced spatial memory impairment in mice.

Methamphetamine (METH) administration results in addiction and memory impairment. Previous studies have suggested that levo-tetrahydropalmatine (l-THP), an alkaloid purified from the Chinese herb Corydalis, attenuates the behavioral changes induced by METH. Therefore, in this study, we explored whether l-THP could also protect against the METH-induced memory impairment examined using the Morris water maze (MWM). We found that low dose of METH (1.0 mg/kg) treated for 20 consecutive days prior to the MWM experiment impaired spatial memory retention but not acquisition in mice. In addition, high dose of METH (10.0 mg/kg) treated during the spatial learning phase for five consecutive days impaired both the acquisition and retention of spatial memory. Moreover, both of these impairments induced by METH were reversed by l-THP treatment, indicating a potential protective role of l-THP in METH use.

Effects of immobilization stress on emotional behaviors in dopamine D3 receptor knockout mice.

A central problem in understanding the dopamine system in anxiety and depression is to specify functions of different members of the dopamine receptor family. Recent studies have reported that the dopamine D2/D3 receptor agonist pramipexole exerts an antidepressant-like effect in the chronic mild stress model and in the behavioral despair model, suggesting dopamine D3 receptor may be an important target for antidepressant actions. The aim of the present study was to examine the role of dopamine D3 receptor on the anxiety-like and depression-like behaviors induced by immobilization stress. We subjected D3 receptor knockout (D3KO) mice to a series of behavioral paradigms after acute (1 h) or chronic (1 h a day for 14 days) immobilization stress. The results showed that immobilization stress significantly altered the anxiety-like behaviors (open field test and elevated plus maze) and depression-like behaviors (tail suspension test) in both D3KO mice and their wild-type littermates. Moreover, further analysis of the data indicated that the D3KO mice, but not their littermates, failed to show a change in immobility time in the tail suspension test after the acute and chronic stress as compared to intact controls, suggesting an increased resistance to the immobilization stress given before behavioral tests. Although our study did not suggest a significant role of D3 receptor in regulating basal anxiety-like and depression-like behaviors, it demonstrated the mice lacking D3 receptor might be more resistant to stressful procedure than their WT littermates.

Distinct roles of methamphetamine in modulating spatial memory consolidation, retrieval, reconsolidation and the accompanying changes of ERK and CREB activation in hippocampus and prefrontal cortex.

Drugs of abuse modulated learning and memory in humans yet the underlying mechanism remained unclear. The extracellular signal-regulated kinase (ERK) and the transcription factor cAMP response element-binding protein (CREB) were involved in neuroplastic changes associated with learning and memory. In the current study, we used a Morris water maze to examine the effect of methamphetamine (METH) on different processes of spatial memory in mice. We then investigated the status of ERK and CREB in the hippocampus and prefrontal cortex (PFC). We found that 1.0 mg/kg dose of METH facilitated spatial memory consolidation when it was injected immediately after the last learning trial. In contrast, the same dose of METH had no effect on spatial memory retrieval when it was injected 30 min before the test. Furthermore, 1.0 mg/kg dose of METH injected immediately after retrieval had no effect on spatial memory reconsolidation. Activation of both ERK and CREB in the hippocampus was found following memory consolidation but not after retrieval or reconsolidation in METH-treated mouse groups. In contrast, activation of both ERK and CREB in the PFC was found following memory retrieval but not other processes in METH-treated mouse groups. These results suggested that METH facilitated spatial memory consolidation but not retrieval or reconsolidation. Moreover, activation of the ERK and CREB signaling pathway in the hippocampus might be involved in METH-induced spatial memory changes.