Mechanical trauma can (MT) cause secondary injury, such as cardiomyocyte apoptosis and cardiac dysfunction has been reported. However, the effects of mechanical trauma on gastrointestinal tract is unclear. This study aims to observe the main location and time of gastrointestinal tract injury caused by non-directional trauma and explain the reason of the increase of LPS in blood caused by mechanical injury. Morphological changes in the stomach, ileum and cecum at different time points after MT were observed in this experiment. The results reveal that the injury to the cecal mucosa in the rats was more obvious than that in the ileum and the stomach. The cecal epithelial cell junction was significantly widened at 20 min after MT, and the plasma LPS and D-lactic acid concentrations increased significantly at the same time point. In addition, some bacterial structures in the widened intercellular space and near the capillary wall of the cecal mucosa were detected at 12 h after MT. This finding suggests that the main reason for the increase in LPS in plasma after MT is cecal mucosal injury. This study is important for the early intervention of the gastrointestinal tract to prevent secondary injury after MT.

Brain-derived neurotrophic factor (BDNF) is a biomarker of depression. Recent studies have found adenosine deaminase acting on RNA1 (ADAR1) is a novel target being sensitive to stress at epigenetic level. The epigenetic regulation mechanism of stress-related depression is still unclear so far. To explore the potential regulating mechanism of ADAR1 on BDNF, over and low expression of ADAR1 in PC12 and SH-SY5Y cell lines are prepared. In the meanwhile, chronic unpredictable stress (CUS) mice are treated with ADAR1 inducer (interferon-γ, IFN-γ). ADAR1 regulates BDNF expression, which is proven by that over and low expressions of ADAR1 increase and decrease BDNF mRNA and protein respectively in vitro. Additionally, ADAR1 inducer alleviates the depressive-like behavior of CUS mice by recovering the decreased BDNF protein in brain and serum. Moreover, over and low expressions of ADAR1 reduce and enhance microRNA-432 (miR-432) expression respectively in vitro. Furtherly, over and low miR-432 expressions lead to decreased and increased BDNF and ADAR1 mRNA, protein and immunoreactivity respectively in vitro. The above results demonstrate that ADAR1 is involved in antidepressant action by regulating BDNF via miR-432. Those novel findings can provide a new idea for the study of epigenetic regulation mechanism, early diagnosis, and effective treatment of stress-related depression.

Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and circ_0000418 in mediating the antidepressant action of ADAR1. We demonstrate that the ADAR1 inducer (IFN-γ) alleviates the depressive-like behaviors of BALB/c mice treated with chronic unpredictable stress (CUS) exposure. Moreover, both in vivo and in vitro studies show that ADAR1 differently impacts miR-432 and circ_0000418 expressions. Furthermore, the in vitro results demonstrate that circ_0000418 oppositely affects BDNF expression. Together, our results indicate that ADAR1 affects CUS-induced depressive-like behavior and BDNF expression by acting on miR-432 and circ_0000418. Elucidation of this new molecular mechanism will not only provide insights into further understanding the important role of ADAR1 in stress-induced depressive-like behavior but also suggest a potential therapeutic strategy for developing novel anti-depressive drugs.

GABA B receptor (GABA B R) antagonists are known to have antidepressant effects. TWIK-related potassium channel-1 (TREK-1) plays a role in GABA B R signaling. However, the role of TREK-1 in the antidepressant actions of GABA B R antagonist is still unclear. This study aimed to investigate whether TREK-1 mediates the antidepressant actions of GABA B R antagonist. To investigate this hypothesis, chronic unpredictable stress rats were treated with a GABA B R antagonist, GABA B R agonist, or TREK-1 blocker. Depression-like behavior was assessed by open field tests and sucrose preference tests. GABA B R and TREK-1 protein levels were measured by western blotting. The results demonstrated that the GABA B R antagonist alleviated depression-like behavior and reversed the decrease in hippocampal TREK-1 protein expression that characterizes chronic unpredictable stress rats. Conversely, the GABA B R agonist exacerbated depression-like behavior and further decreased hippocampal TREK-1 protein expression. In addition, the TREK-1 blocker alleviated the depression-like behavior of chronic unpredictable stress rats and increased hippocampal TREK-1 protein expression. These results suggest that the alleviative effects of the GABA B receptor antagonist on depression-like behavior in chronic unpredictable stress rats are at least partially mediated through TREK-1. These novel findings will be helpful for the clinical therapy of depression.

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

目的 研究高压氧对急性一氧化碳中毒大鼠心肌损伤的保护作用.方法 将大鼠随机分为正常对照组(NC组),急性一氧化碳中毒组(CO-P组),高压氧治疗组(HBO组).采用分次腹腔注射法建立急性一氧化碳中毒大鼠模型,对照组大鼠腹腔注射同等剂量空气,高压氧组大鼠给予高压氧治疗15天,每天1次.CO-P组和HBO组于CO染毒前,第1、2、3、4次CO注射术后1h,第3、7、15天,描记心电图.于染毒后第1天和第16天应用电镜观察各组大鼠心肌超微结构改变.结果 心肌超微结构:CO-P组第1天可见心肌纤维排列紊乱,线粒体肿胀等现象;第16天线粒体腔和嵴间隙略增大.HBO组第1天可见线粒体呈轻度肿胀改变等现象,第16天超微结构已恢复正常.ECG:与NC组比较,CO-P组第4次CO注射后1h、第3、7天和HBO组第3天ST段分别抬高(0.34±0.16)mv,(0.27±0.18)my,(0.20±0.08)my,(0.21±0.11)mv(P ＜0.01);与CO-P组第4次CO注射后1h比较,CO-P组第3、7、15天和HBO组第3、7、15天ST段均显著降低(P＜0.01);与NC组比较,CO-P组第15天和HBO组第7、15天ST段改变基本恢复(P＞0.01).结论 HBO可以显著减轻CO-P大鼠心肌超微结构的损伤程度;CO-P大鼠心电图ST段改变都是可逆的,高压氧治疗可加速ST段下降持续时间及ST段下降幅度,加快心肌损伤的恢复,对心脏有明显的保护作用.

Introduction:Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior. Methods:We evaluated 21-day-old BALB/c mice with and without isolation for aggressive behavior using a resident-intruder test. Immune-reactivity and protein expression of ADAR1 (p110) were measured using immunohistochemistry and Western blotting. Htr2c RNA editing was evaluated using pyrosequencing. In addition, the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 was used to treat the isolated mice, and the performance of both treatments on the behavior, ADAR1 (p110) expression, and Htr2c RNA editing in isolated mice was examined. Results:Both the protein expression and immune-reactivity of ADAR1 (p110) in the amygdala decreased, but the percentage of Htr2c RNA editing at A and B sites of amygdala only showed a moderate increase in isolated BALB/c mice with enhanced aggressive behavior compared to the age-matched group-housed BALB/c mice. Additionally, treatment with the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered the enhanced aggressive behavior of isolated mice and returned the protein expression and immune-reactivity of ADAR1 (p110) back to the normal level. Moreover, compared to the age-matched isolated mice treated with physiological saline, isolated mice treated with 5-HT 2C R inverse agonist SB206553 showed a lower percentage of Htr2c RNA editing at both A and B sites, and the same result occurred in isolated mice treated with 5-HT 2C R antagonist SB243213 at B site of Htr2c RNA editing. Conclusions:The 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered increased aggressive behavior of isolated BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing.

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

目的 观察白杨素对机械性创伤(MT)引起的大鼠继发性心肌损伤的保护作用,并探究其机制.方法 将大鼠分为对照组、创伤组、创伤给药组(注射白杨素)和创伤溶剂组(注射DMSO),每组5只.检测左心室舒缩压力;TUNEL检测心肌细胞凋亡;MTT比色法检测细胞增殖;ELISA检测肿瘤坏死因子 α(TNF-α)表达量;DCFH-DA法测定活性氧(ROS)数量;激光共聚焦显微镜观察心肌细胞内Ca2+浓度.结果 与对照组相比,创伤组血流动力学参数LVDP、MAP、+dP/dTmax和-dP/dTmax均显著下降(P<0.01);心肌细胞凋亡指数显著上升(P<0.01);TNF-α诱导细胞炎性反应下细胞存活率明显下降(P<0.01);TNF-α含量和ROS水平均上升(P<0.01).而白杨素组相比于创伤组,心功能各指标均显著上升(P<0.01);心肌细胞凋亡指数显著下降(P<0.01);TNF-α诱导细胞炎性反应下细胞存活率明显上升(P<0.01);TNF-α含量和ROS水平均下降(P<0.01).结论 MT导致心肌损伤时白杨素通过抑制TNF-α和ROS的过量释放及细胞内钙超载,改善心肌细胞的凋亡而发挥心脏保护作用.

Introduction Social isolation induces depressive-like behavior in animals and humans by impacting RNA editing, but the detailed mechanisms are still unknown. The purpose of this study was to explore how an ADAR1 (RNA-editing enzyme) inducer and inhibitor may impact the isolation-induced depressive-like behavior of mice and to identify new therapeutic targets for the development of an effective solution for the recovery from depressive-like behavior in socially isolated animals and humans. Methods Twenty-one-day-old BALB/c mice with and without isolation treatment were evaluated for depressive-like behavior by open-field tests, tail suspension tests, and forced swimming tests. Immunohistochemistry and Western blots were used to measure the immunoreactivity and protein expression of ADAR1 (p110). In addition, the isolated mice were treated with an ADAR1 inducer (IFN-γ) or inhibitor (EHNA). The performance of both treatments on the behavior of and ADAR1 (p110) expression in isolated mice was examined. Results Both the immunoreactivity and protein expression of ADAR1 (p110) in the prefrontal cortex decreased in isolated BALB/c mice with depressive-like behavior compared to those of the age-matched, gregarious BALB/c mice. Additionally, the treatments with ADAR1 inducer or inhibitor improved or aggravated depressive-like behavior in isolated mice, respectively. Furthermore, the ADAR1 inducer returned the immunoreactivity and protein expression of ADAR1 (p110) back to the normal level. Conclusion The ADAR1 inducer attenuated the effects of social isolation on depressive-like behavior and ADAR1 (p110) in BALB/c mice.

Curcumin, a phytochemical component derived from turmeric (Carcuma longa), has been extensively investigated because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play critical roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This research was designed to identify the protective effect of curcumin on posttraumatic cardiac dysfunction and investigate its underlying mechanism. Noble–Collip drum was used to prepare a mechanical trauma (MT) model of rats, and the hemodynamic responses of traumatized rats were observed by ventricular intubation 12h after trauma. Myocardial apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. Tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) generated by monocytes and myocardial cells were identified through enzyme-linked immunosorbent assay (ELISA), and the intracellular alteration of Ca2+ in cardiomyocytes was examined through confocal microscopy. In vivo, curcumin effectively ameliorated MT-induced secondary cardiac dysfunction and significantly decreased the apoptotic indices of the traumatized myocardial cells. In vitro, curcumin inhibited TNF-α production by monocytes and reduced the circulating TNF-α levels. With curcumin pretreatment, ROS production and Ca2+ overload in H9c2 cells were attenuated when these cells were incubated with traumatic plasma. Therefore, curcumin can effectively ameliorate MT-induced cardiac dysfunction mainly by inhibiting systemic inflammatory responses and by weakening oxidative stress reaction and Ca2+ overload in cardiomyocytes.

医学人才不仅掌握医学知识和临床技能还要具备科研能力.通过多元化教学模式,包括引导式教学、启发式教学、基于任务的学习、基于问题的学习、双语教学及应用辩证唯物主义世界观来进一步培养学生的科研思维,探讨提高大学生科研素质的最佳教学模式.

Multiple organ dysfunctional syndrome secondary to mechanical trauma (MT) has attracted considerable research attention. The heart is one of the most important organs of the body, and secondary cardiac insufficiency caused by MT seriously affects the quality of life. This study aims to investigate whether proanthocyanidin can alleviate myocardial injury and improve heart function in the process of MT leading to secondary cardiac insufficiency. Noble-Collip drum wasused to prepare MT model in rats. And myocardial apoptosis index was calculated after TUNEL staining. Ventricular intubation was employed to detect heart function. Changes in myocardial ultrastructure were observed using an electron microscope. ELISA was used to detect the content of TNF-α and reactive oxygen species generated from monocytes and cardiomyocytes. The changes in Ca2+ concentration in cardiomyocyte were observed by confocal microscope. Compared with trauma group, the administration group had a decreased apoptosis index of cardiomyocytes, and increased ±dp/dtmax. Meanwhile, proanthocyanidin can inhibit monocytes' TNF-α production, and reduce plasma TNF-α concentration. Moreover, proanthocyanidin can attenuate the excessive oxidative stress reaction of cardiomyocyte, and inhibit calcium overload in cardiomyocytes. In conclusion, proanthocyanidin can effectively ease myocardial damage and improve cardiac function, through anti-inflammatory and antioxidant effects in secondary cardiac insufficiency caused by MT.

肿瘤干细胞学说是目前肿瘤研究中最主要的学说之一,认为其与肿瘤的发生发展密切相关.肿瘤干细胞(cancer stem cells,CSCs)与干细胞的特点极为相似.虽然数量稀少但对于肿瘤的起源、复发和转移有决定性作用.本文将对肿瘤干细胞的起源、增殖、转移及其产生免疫耐受等生物学特性的研究进行相关概述,旨在为肿瘤干细胞在临床治疗中的应用提供理论依据.

It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models.However, detailed mechanisms are not clear yet.ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function.We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit.To prove our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot.Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice.In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex.Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence.In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit.This finding may open a window to better understand the reasons (e.g.epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.

目的 观察槲皮素对机械性创伤(MT)造成大鼠继发性心肌细胞及心脏功能损伤的保护效果,同时探究其作用机制.方法 实验分为在体实验和离体实验.将120只成年雄性SD大鼠按随机数字表法分为4组,分别为正常组、创伤组、创伤+槲皮素和创伤+溶剂组.先后应用小动物定量创伤仪制备大鼠MT模型;经右颈总动脉向左心室内插管,记录左心室舒缩压力变化,检测大鼠心功能,初步研究槲皮素对心脏的保护作用;通过MTT比色法检测槲皮素对创伤诱导的H9c2细胞存活率的影响,确定槲皮素对心脏的保护效果;在槲皮素的保护机制研究中,TUNEL染色后计算心肌细胞凋亡指数,以评估心肌细胞的凋亡状况;通过酶标仪检测H9c2细胞在加入槲皮素前后产生活性氧(ROS)自由基的量的变化;激光共聚焦显微镜下观察测定经Fluo-4AM标记的心肌细胞内Ca2+的浓度变化,从而初步探讨槲皮素发挥保护作用的机制.结果 ①心功能指标LVDP、+dP/dtmax、-dP/dtmax显示,创伤组、创伤+溶剂组与正常组比较均明显下降,而创伤+槲皮素组较创伤组升高(P＜0.01).②MTT检测发现,在一定的浓度范围内,槲皮素对H9c2细胞没有细胞毒性作用,并且可明显阻碍创伤血清对H9c2细胞的损伤.③MT后通过对正常组、创伤组、创伤+槲皮素组和创伤+溶剂组心肌细胞凋亡指数的检测,发现创伤+槲皮素组与创伤组比较凋亡指数明显降低(P＜0.01).④通过对H9c2细胞内ROS的检测,发现槲皮素能够减低MT后细胞内ROS的产生.⑤通过对心肌细胞内钙浓度变化的检测,发现MT后Ca2+浓度上升,给予一定浓度槲皮素后Ca2+浓度下降.结论 在一定的浓度范围内,槲皮素能够降低MT后产生的ROS自由基,抑制Ca2+内流,继而降低心肌细胞凋亡,改善MT后心脏功能,发挥心脏保护作用.

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.

It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models.However, detailed mechanisms are not clear yet.ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function.We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit.To prove our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot.Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice.In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex.Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence.In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit.This finding may open a window to better understand the reasons (e.g.epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.

It has been reported that social isolation stress could be a key factor that leads to cognitive deficit for both humans and rodent models. However, detailed mechanisms are not yet clear. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We have hypothesized that social isolation stress may impact the expression of ADAR1 in the brain of mice with cognitive deficit. To test our hypothesis, we evaluated the cognition ability of mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expression in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress induced spatial and non-spatial cognition deficits of the tested mice. In addition, social isolation significantly increased both the immunoreactivity and protein expression of ADAR1 (p110) in the hippocampus and frontal cortex. Furthermore, re-socialization could not only recover the cognition deficits, but also bring ADAR1 (p110) immunoreactivity of hippocampus and frontal cortex, as well as ADAR1 (p110) protein expression of hippocampus back to the normal level for the isolated mice in adolescence. In conclusion, social isolation stress significantly increases ADAR1 (p110) expression in the hippocampus and frontal cortex of the mice with cognitive deficit. This finding may open a window to better understand the reasons (e.g., epigenetic change) that are responsible for social isolation-induced cognitive deficit and help the development of novel therapies for the resulted diseases.