丹芪水提液对泼尼松性大鼠脑损害的防治作用

目的 :探讨长期超生理剂量糖皮质激素对大鼠所致的脑损害特点 ,并观察丹芪水提液对其防治作用。方法 :SD大鼠予泼尼松 2 .7mg·kg-1灌胃 ,每日 1次 ,连续 12周 ,同时用丹芪水提液高、中、低 3种剂量 (2 .5 ,5 .0 ,10 .0g·kg-1·d-1)进行治疗。测试大鼠迷宫记忆力 ,检测脑匀浆与神经活动有关的酶含量并对脑组织的形态进行计量学分析。结果 :长期使用糖皮质激素后 ,大鼠迷宫正确率明显下降 ;脑匀浆中超氧化物歧化酶 (SOD)含量降低而单胺氧化酶 (MAO)含量增高 (P <0 .0 5 ) ;海马神经元出现明显的变性坏死 ,皮层结构紊乱 ;丹芪水提液 3组均可有效预防泼尼松所致的大鼠中枢神经系统的功能和结构的改变 ,明显减少糖皮质激素长期应用所造成的不良反应。结论 :长期应用泼尼松可对大鼠造成脑损害 ,丹芪水提液对其有较好的对抗作用。     

单次皮质酮注射对小鼠情绪症状与认知功能的影响

目的通过单次皮下注射不同剂量的皮质酮,模拟不同程度急性应激状态,进而评价小鼠情绪症状与认知功能的变化。方法 SPF级BABL/c小鼠经自主活动性筛选后,按自主活动及体重随机分为正常对照组、皮质酮给药组(50,100,200 mg·kg~(-1))。行为学实验均在皮质酮注射1 h后进行。采用旷场实验、高架十字迷宫实验和悬尾实验评价皮质酮模拟急性应激对小鼠情绪症状的影响;采用新物体识别实验和Morris水迷宫实验评价皮质酮模拟急性应激对小鼠认知功能的影响。结果与对照组相比,皮质酮50 mg·kg~(-1)剂量组没有引起小鼠情绪及认知行为的明显改变。皮质酮100 mg·kg~(-1)剂量组显著降低小鼠在旷场实验中进入中心区域的时间(P<0.05)与次数(P<0.01);对高架十字迷宫和悬尾实验没有明显影响;可显著降低小鼠对新物体的偏好指数(P<0.05)以及水迷宫实验中的目标象限停留时间(P<0.05)及目标象限运动距离(P<0.01)。当皮质酮剂量达到200 mg·kg-1时可显著影响小鼠在旷场中活动的总距离。结论单次皮下注射皮质酮100 mg·kg~(-1)可介导小鼠出现焦虑样精神障碍以及物体识别记忆和空间记忆等认知功能损伤,可用于抗应激药物的筛选和相关机制研究。     

苯妥英钠对发育期小鼠学习行为的影响

<正> 近年来,抗癫痫药物对认知功能毒副作用的研究颇受瞩目。临床研究表明,苯妥英钠(diphenylhy-dantoin,DPH)对认知功能具有损害作用,但在癫痫病人的研究中,由于癫痫本身常伴有认知功能障碍,因此很难将结果仅归于药物因素;正常志愿者尤其儿童无法作长期服药观察。本文用正常发育期小鼠,探讨DPH长期给药对迷宫和跳台两种学习行为的影响。     

“肝失疏泄致脑老化”的情绪心理学解读

脑老化相关疾病如痴呆等引起的认知功能下降甚至障碍,严重影响老年人的独立生活能力,给家庭和社会带来沉重负担,已成为全世界共同的医学乃至社会问题。中医学认为,肝主疏泄,调畅情志,若情志不畅则影响肝的疏泄功能,气机失于调达,以致诸病丛生。因此,"肝失疏泄致脑老化"可以视为不良情绪损伤认知功能的问题。《景岳全书》载曰:"痴呆症……,或以郁结,或以不遂,或以思虑,或以惊恐而渐痴呆。"认为不良情绪可以导致痴呆;《辨证录·呆病门》亦曰:"呆病之成,必有其因。大约其始也,起于肝气之郁……",明确指出肝气郁滞可能是健忘、痴呆的始动因素。传统中医学把情志分属五脏,认为"五志伤五脏",但现代临床和文献研究认为,当今社会条件下情志致病的基本方式是多种情志刺激交织组合,首先伤肝。肝失疏泄,气机运行失调,影响精气血津液的生成、运行和输布,导致气血匮乏或痰阻血瘀,气血无以上供于脑,导致脑失濡养,生机下降而逐渐老化。"肝失疏泄致脑老化"是中医情志病因学说的重要体现。情绪心理学是研究情绪的一个心理学分支。从现代科学的角度认识情绪,对身心疾病的研究有重要价值。情绪心理学认为情绪是机体对客观存在的反应,它和认知一样都是脑的功能。情绪作为一种状态,经常存在于脑的活动过程中,为认知提供操作的背景,影响注意的集中,记忆的储存、提取以及思维加工。不同的情绪维度对认知的影响各异。研究发现,负性情绪下的智能操作质量不如正性情绪,高焦虑、抑郁者具有较低的处理速度、注意转移和抑制能力。弗洛伊德认为焦虑、抑郁都是由心理能量压抑所引起,这与中医肝郁的肝失疏泄有着异曲同工之妙。这些研究成果说明,与"肝失疏泄"相关的负性情绪可以降低认知功能。生理应激是构成情绪反应不可或缺的部分。肝脏象的现代研究认为,肝主疏泄调畅情志的过程是神经-内分泌-免疫网络调节机体的过程,涉及中枢、外周的多个层次、靶点及环节的变化。长期存在的负性情绪引起神经递质、糖皮质激素等神经化学物质分泌的紊乱,从而影响中枢神经的结构和功能。于艳红认为这种由情志刺激引起的神经化学物质含量和功能的改变是导致脏腑气机紊乱而致病的主要微观机制。焦虑、抑郁个体,以及对负性情绪敏感的高神经质人群存在神经-内分泌-免疫功能紊乱,可能"肝失疏泄"引起认知功能衰退的重要机制。研究认为负性情绪是认知功能衰退的危险因素。神经质是与情绪相关的人格维度,高神经质者往往情绪调节不良,容易感受负性情绪,存在"肝失疏泄"的状态。据调查,高神经质人群的认知功能比低神经质者下降更快,患痴呆的风险更高。可见长期负性情绪引起肝失疏泄,影响认知功能,加速脑老化是在人群中确实存在的医学现象。这些研究成果支持"肝失疏泄致脑老化"理论。中医学是中华民族医疗智慧的结晶,从现代科学角度对传统中医理论进行发掘和探索有助于中医的现代化,使中医焕发新的生机,从而更好地为人类健康事业服务。     

吡格列酮改善脑室注射链脲霉素诱导的小鼠认知损害及其机制的研究

目的:研究吡格列酮对脑室注射链脲霉素诱导小鼠认知损害的影响及其作用机制。方法:采用双侧脑室注射链脲霉素(0.5 mg/kg)制备小鼠认知损害模型,吡格列酮连续灌胃给药20 d,每天1次,采用Morris水迷宫和Y迷宫试验评价认知功能,并测定脑内乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(ChAT)以及外周血糖水平。结果:吡格列酮(9 mg.kg-1.d-1,18 mg.kg-1.d-1)能显著缩短小鼠在可见平台试验中寻找平台的潜伏期,增加空间探索试验中平台所在象限停留时间百分率;增加Y迷宫测试中的正确反应次数。吡格列酮还能显著增加小鼠脑组织海马区和皮层区Ach含量,降低AchE活性,并且增加ChAT活性,但对动物外周血糖无明显影响。结论:吡格列酮可通过降低AchE活性和提高ChAT活性,使小鼠脑内Ach含量增加,从而改善脑室注射链脲霉素所致的小鼠认知损害。     

双功能融合蛋白RDP-BDNF对东莨菪碱所致认知功能障碍小鼠学习记忆的影响

目的研究融合蛋白RDP-BDNF穿越血脑屏障和神经保护活性的双重功能,为脑部疾病的治疗提供一种新方法。方法我们将新型穿膜肽狂犬病毒糖蛋白衍生肽(RDP)基因与BDNF基因融合并在大肠杆菌中表达,融合蛋白经尾静脉注射入小鼠体内,用ELISA法检测RDP-BDNF在脑和血清中的时效曲线;另外通过Morris水迷宫法研究融合蛋白对东莨菪碱所致的认知功能障碍小鼠学习记忆的影响,并探究其作用的机制。结果 RDP-BDNF可以穿过血脑屏障,且能提高东莨菪碱所致认知功能障碍小鼠的学习记忆能力。结论通过载体RDP介导实现蛋白质的入脑转运可能为脑部疾病的治疗提供一种新方法。     

高原缺氧对人认知功能的影响及干预措施

我国高原面积广阔,高原环境因其特殊地域事关我国经济建设和国家安全。具有重要军事及经济意义的青藏高原平均海拔>4000 m,空气稀薄、低温干燥等特殊的高原环境对进驻人群的身心健康产生严重威胁。近年来,随着神经科学技术的发展,高原环境对脑认知功能的影响越来越受到关注。本文综述了海拔高度和高原暴露时间对人认知功能的影响,以及改善脑认知功能的直接和间接干预措施和存在的问题等,为平原人急进高原和高原环境下人认知功能的保护、脑力作业能力的保障提供参考。     

吗啡依赖动物戒断后的焦虑情绪变化

本文采用高架十字迷宫模型和Vogel's饮水冲突模型观察吗啡依赖动物自然戒断后18、24、48、72、96、120h的焦虑情绪 ,结果表明吗啡依赖动物自然戒断后48h时的焦虑症状在两种模型上都最为明显 ,丁螺环酮可明显缓解吗啡所致的焦虑情绪。提示高架十字迷宫模型和Vogel's饮水冲突模型可较为客观和准确地反映吗啡所致焦虑情绪。     

高原低氧环境影响抗癫痫药物的研究进展

高原低氧环境通过改变机体胃肠排空速率、器官血流量、药物血浆蛋白结合率、药物代谢酶和转运体表达等影响药物的药代谢动力学过程。癫痫是一种需长期用药的脑部疾病,而大多数抗癫痫药物的治疗指数低、有效血药浓度范围窄。临床上常用治疗药物监测(therapeutic drug monitoring, TDM)来寻找抗癫痫药物的最佳个体化用药方法。该文对临床上常用抗癫痫药及其治疗窗进行归纳总结,并分析高原低氧环境对抗癫痫药物药代动力学的影响,为高原抗癫痫药物临床用药提供参考。     

高压氧综合与单独药物治疗对颈动脉狭窄致认知功能变化的对比研究

通过应用药物联合高压氧及单独药物两种治疗方法,观察其对血管狭窄所致认知功能改变的影响。目的:对比研究药物联合高压氧治疗及单独药物治疗对血管重度狭窄引起的认知功能变化疗效区别。方法:根据入选病例标准选取120例患者,其中60例患者采用药物联合高压氧治疗(综合治疗组:舒降之+高压氧)。60例患者采用单独药物治疗(药物组:阿司匹林+舒降之);治疗前及治疗3个月后对两组患者行简易精神量表评分(MMSE)。结果:治疗3个月后,联合治疗组MMSE评分明显高于治疗前(P<0.01)。药物组MMSE评分与治疗前无明显差别(P>0.05)。治疗3个月后联合治疗组MMSE评分高于药物组(P<0.01)。结论:高压氧综合治疗可有效改善脑循环,改善认知功能;药物治疗(阿司匹林+舒降之)对颈内动脉狭窄引起的认知功能改变无明显疗效。     

Drug enhancement of memory consolidation: historical perspective and neurobiological implications

Introduction

Studies of drug enhancement of cognition began with Lashley’s (Psychobiology 1:141–170, 1917) report that strychnine administered before daily training trials enhanced rats’ maze learning. Many subsequent studies confirmed that finding and found that stimulant drugs also enhance the learning of a wide range of tasks.

Discussion

A central problem in interpreting such findings is that of distinguishing the drug effects on brain processes underlying memory formation from many other possible effects of the drugs on the behavior used to assess learning. The subsequent finding that comparable learning enhancement can be obtained by posttraining drug administration provided compelling evidence that drugs can enhance memory by acting on memory consolidation processes. Such evidence stimulated the investigation of endogenous regulation of memory consolidation by arousal-released adrenal stress hormones.

Conclusion

Considerable evidence now indicates that such hormones regulate memory consolidation via activation of the basolateral amygdala and subsequent influences on many efferent brain regions involved in processing recent experiences. The implications of these findings for the development of cognitive enhancing drugs are discussed.     

Nandrolone abuse decreases anxiety and impairs memory in rats via central androgenic receptors

Anabolic androgenic steroids (AASs) affect areas of the central nervous system, which are involved in emotional and cognitive responses such as sexuality, anxiety, and memory. In the present study we imitated the abuse of AASs by administering high doses of the AAS nandrolone decanoate (ND) to rats. Thereafter rats were exposed to an elevated plus-maze and an olfactory social memory test to evaluate their anxiety-like and cognitive behaviour. To reveal whether these emotional and cognitive changes evoked by ND were caused via direct activation of androgenic receptors (ARs) in the brain, the AR antagonist flutamide (FL) was administered intracerebroventricularly (i.c.v.). Male rats were randomly divided in four groups, one group received 15 mg/kg ND subcutaneously, once daily for 6 wk (ND group). In the second group, in addition to ND, a daily dose of 5 microg FL was injected i.c.v. also for 6 wk (ND+FL group). The third group of rats received only FL and in the control group the vehicle was injected. The ND group clearly spent more time investigating the open arms in the maze test and recognizing the juvenile during the olfactory social memory test in comparison to the control group. In the ND+FL group rats showed similar emotional behaviour and cognitive ability to that of the control group. Injection of FL alone did not affect either anxiety or memory. These results indicate that repeated, high-dose administration of ND decreases anxiety and impairs memory in rats via direct activation of central ARs.     

Effects of estrogen on congnition mood, and degenerative brain diseases

OBJECTIVE: To review research findings on the effects of estrogen on cognition, mood, memory, and degenerative brain disease in women. DATA SOURCES: English-language journal articles published primarily since 1995, retrieved from a MEDLINE search and from bibliographies of selected reviews. STUDY SELECTION: Investigational studies, clinical trials, and review articles examining the effects of estrogen on the central nervous system. DATA SYNTHESIS: Although scientific study of the brain is in its infancy, numerous studies indicate that estrogen is essential to optimal brain function. Estrogen has been shown to increase cerebral blood flow, act as an antiinflammatory agent, enhance activity at neuronal synapses, and exert direct neuroprotective and neurotrophic effects on brain tissue. Through these varied mechanisms, estrogen strongly influences mood and cognition, and the decline of this hormone at menopause can produce significant emotional and cognitive problems in women. CONCLUSION: Pharmacists can educate women about the various mood and memory changes that can occur during perimenopause and how estrogen replacement therapy may lead to improvements in brain function. The potential use of estrogen replacement therapy to reduce the risk of Alzheimer's disease and ease the symptoms of Parkinson's disease could have a profound effect on women, their families, and society as a whole.     

甲硫哒嗪损伤大鼠学习记忆伴随脑β-淀粉样蛋白的升高

目的观察甲硫哒嗪损伤大鼠学习记忆是否伴随脑内β-淀粉样蛋白(β-amyloid protein,Aβ)水平的升高,探讨甲硫哒嗪引起认知功能受损的机制。方法20只大鼠随机分为对照组和甲硫哒嗪组,连续2wk分别腹腔注射生理盐水和治疗剂量的甲硫哒嗪(10mg·kg-1)。用Morris水迷宫测定大鼠学习记忆能力,用放射免疫分析法测脑组织Aβ含量,用免疫组织化学染色检测β-淀粉样前体蛋白(β-amyloid precursor protein,APP)表达,用RT-PCR方法测定脑中3种APP、α及β-分泌酶mRNA表达。结果甲硫哒嗪组大鼠学习记忆能力下降,脑组织Aβ含量升高(P<0.05),是对照组的1.3倍;脑皮质和海马区APP蛋白表达增高(P<0.05);除APP695、α-分泌酶mRNA表达变化无统计学意义外,脑组织APP751和APP770 mRNA表达升高(P<0.05),相对表达量之和是对照组的2.5倍;β-分泌酶mRNA表达升高(P<0.05),是对照组的2.6倍。结论脑内Aβ水平的增加,可能是甲硫哒嗪引起认知功能损害的原因之一。     

Possible dose–side effect relationship of antipsychotic drugs: relevance to cognitive function in schizophrenia

Management of adverse events is a major concern of clinicians who use antipsychotic drugs. The incidence of motor side effects is dose dependent. Atypical antipsychotic drugs are less likely to induce neurologic side effects compared with typical (conventional) antipsychotics, such as haloperidol. Some recent, large-scale studies have shown that the incidence of metabolic side effects often associated with atypical agents does not differ among typical and atypical antipsychotics. Cognitive function, such as verbal learning memory, working memory, executive function, verbal fluency and attention/information processing, is the most influential determinant of outcome in patients with schizophrenia. Atypical antipsychotic drugs have been shown to be more efficacious in treating cognitive disturbances of schizophrenia compared with typical antipsychotic drugs. Serotonin (5-hydroxytryptamine [5-HT]) receptor subtypes, such as the 5-HT_1A receptor, are considered to mediate the ability of antipsychotic drugs to enhance cognition. On the other hand, treatment with some atypical agents, such as risperidone, may deteriorate working memory in some people with early-stage schizophrenia. The paradoxical side effects of these antipsychotic drugs in terms of cognition may be attributable to dose, duration of treatment and type of cognitive domain. Further research will add to the worldwide endeavor to develop more effective psychotropic drugs accompanied with minimal side effects, for the improvement of cognition, adherence and long-term outcome in patients with schizophrenia or other major psychiatric illnesses.     

Eating for pleasure or calories

A changing environment and lifestyle on the background of evolutionary engraved or perinatally imprinted physiological response patterns is the foremost explanation for the current obesity epidemic. However, it is not clear what the mechanisms are by which the modern environment overrides the physiological controls of appetite and homeostatic body weight regulation. Major advances have been made regarding crosstalk between metabolic signals and the cognitive/emotional brain that primarily deals with the environment. On one hand, metabolic signals such as leptin and ghrelin have previously unexpected direct effects on learning and memory, as well as liking and wanting. On the other hand, brain areas involved in reward, cognition, and executive control can override metabolic regulation by talking to the hypothalamus.     

An hypothesis on the role of glucose in the mechanism of action of cognitive enhancers

This review presents evidence that some cognition enhancing drugs produce their beneficial effects on learning and memory by increasing the availability of glucose for uptake and utilization into the brain. The hypothesis further suggests that many cognition enhancing drugs act through a peripheral mechanism rather than directly on the brain. The general hypothesis is supported by four independent and converging pieces of evidence: 1) Some cognition enhancing drugs may not cross the blood-brain barrier, but can still facilitate memory; 2) Some cognition enhancing drugs are effective only when injected peripherally, but not when injected directly into the brain; 3) Many cognition enhancing drugs are not effective after adrenalectomy; 4) Cognitive function is correlated with glucose regulation in aged animals and humans. These four lines of research have implications for the role of glucose in the action of specific cognitive enhancers.     

The ethics of elective psychopharmacology

Pharmacological cognitive enhancers (PCEs) are used to improve cognitive functions, such as attention, learning, memory and planning in patients with impairments in cognition resulting from traumatic brain injury (TBI) or from neuropsychiatric disorders such as Alzheimer's disease (AD), mild cognitive impairment, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Moreover, PCEs have been shown to improve cognition in healthy volunteers with no psychiatric disorders. This article describes the rationale behind the need for their use in neuropsychiatric patients and illustrates how PCEs can ameliorate cognitive impairments, improve quality of life and wellbeing, and therefore reduce the economic burden associated with these disorders. We also describe evidence that PCEs are being used as cognitive enhancers by healthy people. Crucially, as the lifestyle use of these drugs becomes very popular in the healthy population, a final aim is to present an overview of the current and future neuroethical considerations of enhancing the healthy brain. As information regarding their actual use, benefits and harms in various healthy populations is currently lacking, we propose research that aims to obtain relevant empirical data, monitor the short- and long-term effectiveness and side-effects, and initiate accurate surveys to determine current patterns and quantity of usage of PCE drugs by healthy people. Furthermore, in order to instigate a dialogue between neuroethics and neuropsychopharmacology, we urge scientists to explore and communicate the social and ethical implications of their research to the public. Finally, we discuss and highlight other means of enhancing cognition in both patients and healthy adults, including education and physical exercise.     

Pharmacology of human memory and cognition: illustrations from the effects of benzodiazepines and cholinergic drugs

The current research methods, findings and questions that are being addressed in studies of the pharmacology of human memory and cognition are reviewed. Memory is not a unitary function. Neuropsychological studies of brain-damaged memory-impaired patients, as well as neuroimaging and drug studies in normal individuals indicate that different forms of learning and memory are subserved by different brain systems. Animal drug studies have also provided evidence that, while distinct, memory systems are not independent, but operate in close interaction with one another. Recent human studies of benzodiazepines and of cholinergic drugs demonstrate the value of the psychological models and of the experimental paradigms that are available from cognitive sciences for exploring how drugs alter cognitive and memory functions. They also show how drugs can be used as tools for analyzing the distinct neurochemical mechanisms underlying independent cognitive processes, and so find effective drugs rationally from a knowledge of the neurochemical bases of cognition. This research leads to specific recommendations concerning treatments that may improve memory functioning, for instance in Alzheimer's disease.