热休克因子1及多种热休克蛋白在人良性脑膜瘤中的表达

目的探讨人良性脑膜瘤细胞中热休克因子1（HSF1）及热休克蛋白（HSP）HSP27、HSP70和HSP90的表达。方法应用免疫组化法和western blot法检测15例人脑膜瘤原代培养细胞中HSF1、HSP27、HSP70和HSP90蛋白的表达。结果15例人脑膜瘤中，HSF1蛋白以单体形式存在（分子量为80kD左右），阳性率为100％（15／15），HSP27、HSP70和HSP90阳性率分别为40％（6／15）、46．7％（7／15）和53．3％（8／15）。结论人良性脑膜瘤存在HSF1蛋白表达，而HSP27、HSP70和HSP90组成型表达水平低。     

热休克预处理对实验性自身免疫性脑脊髓炎神经细胞凋亡的影响及其机制研究

目的观察热休克预处理（HSP）后实验性自身免疫性脑脊髓炎（EAE）大鼠热休克蛋白70（HSP70）和核因子-KB（NF-KB）的表达及对神经细胞凋亡的影响，探讨其对EAE模型的神经保护作用。方法36只Wistar大鼠随机分为对照组（CON），EAE组和HSP组。EAE组制作成EAE模型；HSP组先给予HSP，24h后再制作成EAE模型；CON组不行特殊处理。观察大鼠神经症状．进行神经功能评分。于免疫后14-17d处死动物，取脊髓行HE染色，检测HSP70、NFKB免疫组化表达及神经细胞的凋亡。结果CON组大鼠没有发病。与EAE组大鼠比较，HSP组大鼠发病率显著降低，起病时间显著延迟，神经功能评分显著降低（均P〈0．05）。EAE组体重增加值较CON组明显减低，HSP后大鼠体重增加值较EAE组显著增加（p〈0．05）。脊髓病理显示HSP组炎性病灶数较EAE组显著减少（p〈0．05）。HSP组与EAE组相比，脊髓内HSP70阳性细胞数显著增加，NF-KB阳性细胞数显著减少，神经细胞凋亡显著抑制（均P〈0．01）。结论HSP对EAE大鼠具有一定的神经保护作用，其机理可能与HSP70表达增加，NF—KB表达受抑制从而导致神经细胞凋亡减少有关。     

热休克蛋白对中枢神经的保护作用

热休克蛋白(HSP)是细胞在应激条件下产生的一类蛋白质,它与细胞的许多病理及生理过程密切相关,近年来研究表明HSP在中枢神经系统中并不是传统上认为的参与神经损伤,相反具有神经保护作用。热休克蛋白家族中几种主要的HSP都具有中枢神经保护作用,而每种HSP的保护作用都具有各自的特异性。由于HSP的中枢神经保护作用,其临床应用前景也成为人们关注的焦点。     

热耐受对鼠脑海马缺血后细胞凋亡的保护

目的　观察热耐受对鼠脑海马缺血再灌流后细胞凋亡的保护作用，并探讨迟发神经元死亡（ Ｄ Ｎ Ｄ） 与细胞凋亡的关系。方法　大鼠前脑缺血１０ ｍｉｎ ，以及在缺血前反复３ 次高热处理，应用 Ｔ Ｕ Ｎ Ｅ Ｌ 技术检测海马缺血区凋亡细胞，并用免疫组化法检测该区 Ｈ Ｓ Ｐ７０ 表达水平。结果　缺血再灌流后，细胞凋亡在 Ｄ Ｎ Ｄ 形态学改变前出现。热耐受后可显著减轻缺血损害导致的细胞凋亡。结论　细胞凋亡是 Ｄ Ｎ Ｄ 的死亡方式之一，热耐受诱导的 Ｈ Ｓ Ｐ７０ 表达增强是其保护细胞、减少凋亡的主要机制。     

干细胞因子对糖尿病小鼠皮层神经元凋亡的保护作用

目的 探讨干细胞因子对糖尿病所致神经元凋亡的干预效应及其可能机制.方法 成年雄性C57小鼠27只,随机分为正常对照组、糖尿病组、糖尿病干细胞因子组,每组9只.用链脲佐菌素建立糖尿病小鼠模型,TUNEL染色反映大脑神经元的凋亡情况,Western blot检测BCL-2、BAX、CASPASE 3及P-ERK/ERK蛋白的表达.结果 与对照组相比,糖尿病小鼠大脑皮层神经元凋亡数量增加且有活性的CASPASE 3表达升高,应用干细胞因子干预后,上述情况可以得到有效的改善.糖尿病小鼠大脑皮层内的BCL-2、BAX均较正常组明显升高,应用于细胞因子后可抑制BAX的表达而对BCL-2无明显影响;相应的BCL-2/BAX比值在正常组和糖尿病组之间无显著性差异存在,但干细胞因子的应用能明显升高其表达.糖尿病小鼠P-ERK表达水平明显降低,应用于细胞因子后可有效增加ERK的磷酸化甚至超过正常水平.结论 干细胞因子可能通过增加ERK的磷酸化而影响BCL-2/BAX的表达发挥对糖尿病神经元的抗凋亡作用.     

慢性应激对海马的影响及其机制

应激是机体在各种内外环境因素及社会、心理因素刺激时所产生的非特异性适应反应。应激时机体稳态失衡,产生神经内分泌、免疫、神经生化等一系列改变,导致器官功能甚至结构的改变。海马是与学习、记忆、认知、行为和情绪密切相关     

热耐受对鼠脑海马缺血后细胞凋亡的保护☆

】　目的　观察热耐受对鼠脑海马缺血再灌流后细胞凋亡的保护作用，并探讨迟发神经元死亡(DND)与细胞凋亡的关系。方法　大鼠前脑缺血10 min，以及在缺血前反复3次高热处理，应用TUNEL技术检测海马缺血区凋亡细胞，并用免疫组化法检测该区HSP70表达水平。结果　缺血再灌流后，细胞凋亡在DND形态学改变前出现。热耐受后可显著减轻缺血损害导致的细胞凋亡。结论　细胞凋亡是DND的死亡方式之一，热耐受诱导的HSP70表达增强是其保护细胞、减少凋亡的主要机制。     

热休克蛋白对多巴胺能神经细胞的保护作用研究

目的探讨热休克蛋白(HSP)对蛋白酶体抑制剂处理的多巴胺能神经细胞的活力以及细胞内包涵体形成的影响。方法将PC12细胞进行热处理,免疫印迹法鉴定热休克蛋白表达,并确定最佳热处理条件;再应用高选择性的蛋白酶体抑制剂Lactacystin处理PC12细胞。MTT方法检测细胞活力,免疫荧光细胞化学染色观察细胞内包涵体形成的变化。结果免疫印迹法证实PC12细胞热处理2h后HSP70水平即开始迅速升高,一直持续至24h,其中4h的HSP70水平表达较高,故选其为最佳观察条件。未经热处理的对照组经5μM、10μM、15μM和20μMLactacystin处理24h后,PC12细胞的活力显著降低,呈剂量依赖性;热处理组的细胞活力比对照组显著升高,两者有显著性差异(P<0.01)。免疫荧光染色显示对照组细胞的胞浆内包涵体明显增多,而热处理组胞浆内包涵体明显减少。结论热休克蛋白能显著增强细胞活力,减少细胞内包涵体形成,对多巴胺能神经元可能有一定的保护作用。     

心理应激、A型行为与急性脑卒中关系的研究

目的使用流行病学和统计学的方法分析心理应激、A型行为与急性脑卒中的关系。方法采用生活事件量表(LES)、A型行为问卷(TABQ)对急性脑出血患者(n=100),急性脑缺血患者(n=150)和正常对照者(n=135)分别进行分析。结果脑梗死组和对照组A型行为构成比较差异无统计学意义(P>0.05);脑出血组和对照组A型行为构成比较,P<0.05;脑梗死组和对照组患者正性生活事件强度间比较,P<0.05;而脑出血组和对照组患者正性生活事件强度比较差异有统计学意义(P>0.05);脑梗死组和对照组患者负性生活事件强度和总生活事件强度间比较,P<0.05,而脑出血组和对照组患者负性生活事件强度总生活事件强度比较P>0.05;而且A型行为与出血性脑卒中发生存在剂量依赖反应关系。结论 A型行为与急性出血性脑卒中的发生可能有关联;心理应激与急性缺血性脑卒中的发生可能有关联。     

热休克蛋白70的功能及其临床应用前景

正热休克蛋白(hot shock proteins,Hsp)为转录调节蛋白热休克因子(hot shock factor,HSF)诱导其相关基因启动子上存在的热休克原件(hot shockelement,HSE)基因而产生的一类蛋白。脑缺血能引发Hsp反应。Hsp70在正常脑组织中表达水平极低,在缺血脑组织神经元中却被诱导表达,尤其在缺血病灶周边,通过与ATP结合能够对错误折叠和未折     

The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia.

BACKGROUND: Depression has a complex bidirectional association with heart disease. Previously we have shown notable cardiovascular changes in the chronic mild stress (CMS) rodent model of depression. Here we investigated the effects of a serotonin-specific reuptake inhibitor on a behavioral index of depression (anhedonia) and cardiac function in rats exposed to CMS. METHODS: Male Sprague-Dawley rats were exposed to either 4 weeks of control conditions or CMS, consisting of unpredictable periods of mild stressors, while being treated concurrently with 4 weeks of daily fluoxetine (10 mg/kg, sc) or vehicle. RESULTS: Chronic fluoxetine treatment prevented anhedonia in rats exposed to CMS, versus the CMS group treated with vehicle. However, treatment with fluoxetine in the CMS group only partially prevented specific cardiovascular changes associated with CMS, including elevated resting heart rate (HR), exaggerated pressor and HR responses to air jet stress, reduced cardiac output and stroke volume, and HR exaggerated responses to beta-adrenergic receptor blockade. CONCLUSIONS: These findings provide evidence that 4 weeks of fluoxetine treatment can prevent behavioral responses and can partially prevent cardiovascular changes associated with CMS, providing insight into the role of serotonin in the link between depression and cardiovascular dysfunction.     

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5 mg/kg) and medium-dose (1 mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress.     

Antidepressant-like effects of embelin and its possible mechanisms of action in chronic unpredictable stress-induced mice

Objectives Embelin, a principal active constituent of embelin ribes burm, has good therapeutic effects on various diseases. To explore the effects and underlying mechanisms of embelin on depression, we made a preliminary study to clarify this issue.

Methods We first used chronic unpredictable stress (CUS) to construct the model of depression in mice. Then, we determined the effects of embelin on CUS-induced behavioral dysfunction using open field test, sucrose preference test, tail suspension test and forced swimming test. Furthermore, we used the biological experiments to evaluate the changes of brain-derived neurotrophic factor (BDNF), oxidative stress, neuronal inflammation and the hypothalamic pituitary adrenal (HPA) axis after embelin treatment.

Results The behavioral tests indicated embelin indeed had efficient antidepressant effects. Moreover, enhanced BDNF expression, decreased oxidative stress markers (TBARS, nitric oxide) activities, elevated antioxidants (total thiol, catalase) expression, decreased pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) expression and normalized the HPA axis activity were found after embelin treatment in CUS-induced mice. Hence, the results of biological experiments confirmed the antidepressant-like effects of embelin.

Discussion These results indicated that embelin can effectively suppress CUS-induced depressive-like behaviors through increasing BDNF expression, preventing brain from oxidative stress and neuronal inflammation, and normalizing the HPA activity.     

The protective role of mindful parenting against child maltreatment and aggressive behavior: an exploratory study among Chinese parent-adolescent dyads

Depression and suicidal behavior are the main causes of disability and morbidity, especially in adolescents living with HIV (ALWHIV). Data regarding these are lacking in Botswana, a country with a predominantly youthful population and ranked among the top four in the world most affected by HIV. Therefore, the present study aimed to estimate the prevalence of depression and suicidal behavior and explore their associated factors in Botswana ALWHIV. Responses were obtained from 622 ALWHIV using the DSM-5 and the Mini-International Neuropsychiatric Interview for Children and Adolescents. The mean age (SD) of the participants was 17.7 (1.60) years and more males (54.3%) participated than females. Depression and suicidal behavior rates among adolescents were 23% and 18.9%, respectively. Female participants were more likely to be depressed (AOR?=?1.96; 95% CI 1.11–3.45) and have suicidal behaviour (AOR?=?6.60; 95% CI 3.19–13.7). Loss of mother (AOR?=?2.87; 95% CI 1.08–7.62) and viral load of 400 copies and above (AOR?=?5.01; 95% CI 2.86–8.78) were associated with depression. Alcohol use disorder (AOR?=?3.82; 95% CI 1.83–7.96) and negative feelings about status (AOR?=?8.79; 95% CI 4.62–16.7) were associated with suicidal behavior. Good support (AOR?=?0.42; 95% CI 0.23–0.76) and increased frequency of religious activities were protective (AOR?=?0.33; 95% CI 0.14–0.79) against depression and suicidal behaviour, respectively. Therefore, routine psychologic screening, which includes identifying psychological stressors and maladaptive coping, family and caregiver support services, and psychosocial support platforms, should be integrated into the management package for ALWHIV in Botswana.     

脑脉泰对慢性脑缺血大鼠认知功能的保护作用及其机制研究

目的研究脑脉泰影响脑组织神经生长因子(NGF)、胶质纤维酸性蛋白(GFAP)的表达,进而改善慢性脑缺血大鼠的认知功能。方法采用大鼠双侧颈总动脉永久结扎法(2-VO)制备慢性脑缺血模型。术后分别给予脑脉泰不同剂量灌胃治疗6 w。应用Morris水迷宫测定大鼠的学习记忆能力、HE染色观察海马CA1区神经元形态、免疫组化方法检测大鼠脑组织NGF及GFAP的表达。结果与假手术组相比,模型组大鼠的学习能力和记忆能力降低,脑组织中NGF表达减少(P<0.01),GFAP表达增多(P<0.01);脑脉泰给药能够改善大鼠的记忆和学习能力,增加脑组织中NGF表达(与模型组相比,低剂量组P<0.05,高剂量组P<0.01),降低GFAP表达(与模型组相比,低、高剂量均为P<0.01)。结论脑脉泰可能通过提高脑组织NGF和降低GFAP表达来改善慢性脑缺血大鼠的认知功能。     

Therapeutic effects of GM1 on Parkinson's disease in rats and its mechanism

Objective: To observe the effects of GM1 on apomorphine (APO)-induced rotational behavior and the expression of inflammatory factors in 6-hydroxydopamine-induced Parkinson's disease (PD) rat models. Methods: Mature and healthy Wistar rats of either sex with body weight of 150–200 g were randomly divided into control group, PD+APO group and PD+APO+GM1 group (10 mg/kg of GM1, intraperitoneally, once a day, for 14 days; each group with 15 rats). PD rat models were prepared by injecting 6-hydroxydopamine into rat's right striatum, and then rotational behavior was induced by intraperitoneal injection of APO 7 days after operation. Rat rotational behavior was observed, and mRNA and protein levels of interleukin-1β (IL-1β) and interleukin-1Ra (IL-1Ra) were determined, respectively, by RT-PCR and Western blot. Results: Compared with PD+APO group, the rotational behavior was significantly relieved in PD+APO+GM1 group (p < 0.05). Compared with control group, mRNA and protein expressions of IL-1βin the striatum significantly increased in PD+APO group (p < 0.05). However, mRNA and protein expressions of IL-1βsignificantly decreased in PD+APO+GM1 group compared with PD+APO group (p < 0.05), but mRNA and protein expressions of IL-1βwere also higher in PD+APO+GM1 group than in control group (p < 0.05). mRNA and protein expressions of IL-1Ra in the striatum were significantly higher in PD+APO+GM1 group than in PD+APO group (p < 0.05). Conclusion: GM1 can inhibit inflammatory reaction through decreasing mRNA and protein expressions of IL-1β and increasing mRNA and protein expressions of IL-1Ra with the therapeutic effects on PD.     

Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice

Microglia are suggested to be involved in several neuropsychiatric diseases. Indeed changes in microglia morphology have been reported in different mouse models of depression. A crucial regulatory system for microglia function is the well-defined CX3C axis. Thus, we aimed to clarify the role of microglia and CX3CR1 in depressive behavior by subjecting CX3CR1-deficient mice to a particular chronic despair model (CDM) paradigm known to exhibit face validity to major depressive disorder. In wild-type mice we observed the development of chronic depressive-like behavior after 5 days of repetitive swim stress. 3D-reconstructions of Iba-1-labeled microglia in the dentate molecular layer revealed that behavioral effects were associated with changes in microglia morphology towards a state of hyper-ramification. Chronic treatment with the anti-depressant venlafaxine ameliorated depression-like behavior and restored microglia morphology. In contrast, CX3CR1 deficient mice showed a clear resistance to either (i) stress-induced depressive-like behavior, (ii) changes in microglia morphology and (iii) antidepressant treatment. Our data point towards a role of hyper-ramified microglia in the etiology of chronic depression. The lack of effects in CX3CR1 deficient mice suggests that microglia hyper-ramification is controlled by neuron-microglia signaling via the CX3C axis. However, it remains to be elucidated how hyper-ramified microglia contribute to depressive-like behavior.     

The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes

Abstract

Objectives: Estrogen replacement therapy can decrease the risk of developing Alzheimer’s disease. Phytoestrogens have been proposed as potential alternatives to estrogen replacement therapy. The purpose of this study was to evaluate the in vitro protective effects of coumestrol on mice astrocytes.

Methods: Different concentrations of coumestrol were tested for their protective efficacy against two toxic insults, lipopolysaccharide (LPS) and amyloid-beta peptide, on astrocytes. The mitochondrial activity of astrocytes was determined, and the protective efficacy and pathway were examined by their specific gene expression and protein change.

Results: The results showed that coumestrol induced a modest but significant increase in viability of astrocytes, while the viability of astrocytes was reduced following exposure to LPS and amyloid-beta peptide. The addition of coumestrol could reverse the toxic effect induced by LPS and amyloid-beta peptide. Both the LPS and amyloid-beta peptide enhanced interleukin 1, interleukin 6, and tumor necrosis factor-alpha synthesis and these effects were inhibited by 10^?9M coumestrol. This effect was more obvious on the LPS-induced inflammation. The estrogen receptor expression was upregulated by coumestrol, while the effect was more obvious on estrogen receptor-beta (ER-beta). These effects can be inhibited by extracellular signal-regulated kinase and c-Jun N-terminal kinase inhibitors but not p38 inhibitor.

Discussion: The current data support a possible role for astrocytes in the mediation of neuroprotection by coumestrol. An indirect extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling pathway to downregulate the expression of interleukin 1, interleukin 6, and the tumor necrosis factor-alpha cytotoxic effect may act in concert with the proposed direct ER-beta biosynethsis pathway to achieve a widespread, global protection of ER-beta positive neurons.