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共102条结果
  • 1.

    【2hr】Heart and Brain Tissue Banks for Research on Co-Occurring Cardiovascular and Neurological/Psychiatric Disorders

    包量

    机译 心脏和脑组织库，用于研究共同发生的心血管疾病和神经疾病/精神疾病
    摘要：Epidemiological studies point to a strong and possibly causal association of psychiatric and neurological disorders with cardiovascular disease (CVD). Mechanistic links between these co-occurring illnesses are not well understood. Better insight into their relationship could help identify novel diagnostic markers and therapeutic targets. For successful translation of basic biomedical research into clinical practice, analyses of postmortem human tissues are essential. However, current tissue banks dedicated to psychiatric and neurological research collect only brain tissue samples deemed most important to the institution's participating investigators. While this practice is often dictated by budget constraints, restricted tissue storage space and other practical reasons, it limits the ability of the biological research community to access and study multiple organ systems relevant to cardiovascular and neuronal systems dysfunction. This problem is worsened when clinical records pertaining to coexistent systemic pathology are not available. To promote further understanding of co-occurring CVD and psychiatric/neurological disorders, efforts should be made to support tissue banks that harvest heart, coronary arteries, and aorta samples as well as brain tissue, from the same subjects.
  • 2.

    【2hr】Hypotheses on Mechanisms Linking Cardiovascular and Psychiatric/Neurological Disorders

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    机译 关于心血管疾病与精神疾病/神经疾病的关联机制的假设
    • 作者：Hari Manev
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：
  • 3.

    【2hr】The Heart-Brain Connection Begets Cardiovascular Psychiatry and Neurology

    包量

    机译 心脑连接引发心血管精神病学和神经病学
    • 作者：Hari Manev
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：
  • 4.

    【2hr】The 5-Lipoxygenase as a Common Pathway for Pathological Brain and Vascular Aging

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    机译 5-Lipoxygenase作为病理性大脑和血管衰老的常见途径
    摘要：Epidemiological studies indicate age as a strong risk factor for developing cardiovascular and neurodegenerative diseases. During the aging process, changes in the expression of particular genes can influence the susceptibility to these diseases. 5-Lipoxygenase (5-LO) by oxidizing fatty acids forms leukotrienes, potent mediators of oxidative and inflammatory reactions, two key pathogenic events in both clinical settings. This enzyme is widely distributed in the cardiovascular as well as in the central nervous system, where its expression levels increase with age, suggesting that it may be involved in their diseases of aging. The central theme of this article is that during aging, 5-LO acts as biologic link between different stressors and the development of cardiovascular and neurodegenerative diseases. We hypothesize that the age-dependent upregulation of 5-LO represents a “priming” factor in the vasculature as well as in the brain, where a subsequent exposure to triggering stimuli (i.e., infections) leads to an abnormal chronic inflammatory reaction, and ultimately results in increased organ vulnerability and functional deficits.
  • 5.

    【2hr】Interleukin-10: A Key Cytokine in Depression?

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    机译 白介素10：抑郁症的关键细胞因子？
    摘要：An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy.
  • 6.

    【2hr】Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder

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    机译 打破血脑屏障作为精神疾病的大门
    摘要：The mechanisms underlying the development and progression of psychiatric illnesses are only partially known. Clinical data suggest blood-brain barrier (BBB) breakdown and inflammation are involved in some patients groups. Here we put forward the “BBB hypothesis” and abnormal blood-brain communication as key mechanisms leading to neuronal dysfunction underlying disturbed cognition, mood, and behavior. Based on accumulating clinical data and animal experiments, we propose that events within the “neurovascular unit” are initiated by a focal BBB breakdown, and are associated with dysfunction of brain astrocytes, a local inflammatory response, pathological synaptic plasticity, and increased network connectivity. Our hypothesis should be validated in animal models of psychiatric diseases and BBB breakdown. Recently developed imaging approaches open the opportunity to challenge our hypothesis in patients. We propose that molecular mechanisms controlling BBB permeability, astrocytic functions, and inflammation may become novel targets for the prevention and treatment of psychiatric disorders.
  • 7.

    【2hr】Do Neural Cells Communicate with Endothelial Cells via Secretory Exosomes and Microvesicles?

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    机译 神经细胞通过分泌性外泌体和微泡与内皮细胞通讯吗？
    • 作者：Neil R. Smalheiser
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：Neurons, glial, cells, and brain tumor cells tissues release small vesicles (secretory exosomes and microvesicles), which may represent a novel mechanism by which neuronal activity could influence angiogenesis within the embryonic and mature brain. If CNS-derived vesicles can enter the bloodstream as well, they may communicate with endothelial cells in the peripheral circulation and with cells concerned with immune surveillance.
  • 8.

    【2hr】Chromatin from Peripheral Blood Mononuclear Cells as Biomarkers for Epigenetic Abnormalities in Schizophrenia

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    机译 来自外周血单个核细胞的染色质作为精神分裂症表观遗传异常的生物标记
    摘要：Background. Studies have implicated abnormalities in epigenetic gene regulation in schizophrenia. Presentation. We hypothesize that identifying abnormalities in chromatin structure and the epigenetic machinery in peripheral blood mononuclear cells (PBMC) from schizophrenia patients could (a) help characterize a subset of schizophrenia patients and (b) lead to targeted pharmacological interventions. Testing. Investigate the relationship between clinical symptoms, demographics, hormonal fluctuations, substance abuse, disease characteristics across the major mental illnesses, and epigenetic parameters in PBMC. In addition, examine the effects of individual antipsychotics, mood stabilizers, as well as experimental agents both as clinically prescribed as well as in cultured PBMC to understand the effects of these agents on chromatin. Implications. If PBMC could serve as a reliable model of overall epigenetic mechanisms then this could lead to a “biomarker” approach to revealing pathological chromatin state in schizophrenia. This approach may provide an informed method for selecting chromatin modifying agents for psychiatric disorders.
  • 9.

    【2hr】Possible Role of Platelet GluR1 Receptors in Comorbid Depression and Cardiovascular Disease

    包量

    机译 血小板GluR1受体在合并抑郁症和心血管疾病中的可能作用
    • 作者：Hu Chen
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：The exact nature of the comorbidity between cardiovascular disease (CVD) and major depressive disorder (MDD) is poorly understood. The proposed mechanisms include various biochemical and molecular pathways as well as health behaviors such as physical inactivity. One possible link between MDD and CVD is increased platelet activity and blood viscosity. Recently, it was discovered that platelets express functional subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, for example, glutamate receptor 1 (GluR1). Here, I propose that this type of AMPA receptor could play a role in comorbid MDD and CVD, and antidepressants may interfere with platelet activation via direct or indirect effects on platelet GluR1 phosphorylation. Testing this hypothesis could provide a novel view on the pathobiological mechanisms of comorbid MDD and CVD. With respect to the recently discovered role of AMPA receptors in regulating platelet activation and thrombosis, it appears that the information about the putative effects of psychoactive AMPA-modifying drugs on platelet AMPA receptors would be critical in evaluating the putative effects of such drugs on CVD.
  • 10.

    【2hr】Serotonin 5-HT2A Receptor Function as a Contributing Factor to Both Neuropsychiatric and Cardiovascular Diseases

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    机译 血清素5-HT2A受体功能是神经精神病学和心血管疾病的一个成因
    • 作者：Charles D. Nichols
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：There are high levels of comorbidity between neuropsychiatric and cardiovascular disorders. A key molecule central to both cognitive and cardiovascular function is the molecule serotonin. In the brain, serotonin modulates neuronal activity and is actively involved in mediating many cognitive functions and behaviors. In the periphery, serotonin is involved in vasoconstriction, inflammation, and cell growth, among other processes. It is hypothesized that one component of the serotonin system, the 5-HT2A receptor, is a common and contributing factor underlying aspects of the comorbidity between neuropsychiatric and cardiovascular disorders. Within the brain this receptor participates in processes such as cognition and working memory, been implicated in effective disorders such as schizophrenia, and mediate the primary effects of hallucinogenic drugs. In the periphery, 5-HT2A receptors have been linked to vasoconstriction and hypertension, and to inflammatory processes that can lead to atherosclerosis.
  • 11.

    【2hr】P2X7 Receptors as a Transducer in the Co-Occurrence of Neurological/Psychiatric and Cardiovascular Disorders: A Hypothesis

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    机译 P2X7受体作为神经，精神疾病和心血管疾病的同时发生的一种传感器：一个假设。
    摘要：Background. Over-stimulation of the purinergic P2X7 receptor may bring about cellular dysfunction and injury in settings of neurodegeneration, chronic inflammation, as well as in psychiatric and cardiovascular diseases. Here we speculate how P2X7 receptor over-activation may lead to the co-occurrence of neurological and psychiatric disorders with cardiovascular disorders. Presentation. We hypothesize that proinflammatory cytokines, in particular interleukin-1β, are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases. Critically, this premise is based on a role for the P2X7 receptor in triggering a rise in these cytokines. Given the broad distribution of P2X7 receptors in nervous, immune, and vascular tissue cells, this receptor is proposed as central in linking the nervous, immune, and cardiovascular systems. Testing. Investigate, retrospectively, whether a bidirectional link can be established between illnesses with a proinflammatory component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular disease, for example, hypertension, and whether patients treated with anti-inflammatory drugs have a lower incidence of disease complications. Positive outcome would indicate a prospective study to evaluate therapeutic efficacy of P2X7 receptor antagonists. Implications. It should be stressed that sufficient direct evidence does not exist at present supporting our hypothesis. However, a positive outcome would encourage the further development of P2X7 receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.
  • 12.

    【2hr】Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs) in Cardiovascular Diseases (CVDs) and Depression: The Missing Link?

    包量

    机译 心血管疾病（CVD）和抑郁症中的Omega-3多不饱和脂肪酸（n-3 PUFA）：缺失的环节？
    摘要：Background. Based on epidemiological data, clinical trials, and meta-analytic reviews, omega-3 polyunsaturated fatty acids (n-3 PUFAs) seem to be a biological link between depression and cardiovascular diseases (CVDs). Presentation. Involvement of n-3 PUFAs in depression and CVDs may be associated with a chronic, low-grade, inflammation. We hypothesize that n-3 PUFAs link depression and CVDs via “PUFA-prostaglandin E2 (PGE2) cascade.” Testing. To further support our hypothesis, case-control studies are needed to test the role of COX2 and PLA2 functions in depression and in CVDs. In addition, the effects of n-3 PUFAs on cardiovascular markers in depression and on depressive symptoms in CVDs should be investigated in clinical trials. Finally, the effects of manipulating COX2 and PLA2 functions on depression-like behaviors and cardiovascular functions could be explored in animal studies. Implications. n-3 PUFAs might be a promising treatment for both cardiovascular diseases and depression via its anti-inflammatory, cardioprotective, and neuroprotective effects.
  • 13.

    【2hr】Cardiovascular Disease and Psychiatric Comorbidity: The Potential Role of Perseverative Cognition

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    机译 心血管疾病和精神病合并症：持久性认知的潜在作用
    摘要：The high comorbidity between psychiatric disorders and cardiovascular disease has received increasing attention, yet little is known about the processes linking the two. One plausible contributing mechanism is the tendency of those with psychiatric disorders to ruminate on stressful events. This phenomenon, sometimes called perseverative cognition, can extend the psychological and physiological effects of stress, which could contribute to cardiovascular disease etiology. In this paper, we discuss the potential role of perseverative cognition in mediating the relationship between psychiatric illness and cardiovascular disease. Rumination can delay physiological recovery from acute stress, which in turn has been found to predict future cardiovascular health. This delayed recovery could act as a mechanism in the longitudinal link between worry and cardiovascular health. The cognitive inflexibility that characterizes mood and anxiety disorders may then contribute to disease not by producing greater reactivity, but instead through extending activation, increasing the risks for cardiovascular damage.
  • 14.

    【2hr】Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and Cardiovascular Disorders

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    机译 MicroRNA调控的通路在合并性神经系统和心血管疾病中的假定作用。
    摘要：Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure. Here, the hypothesis of how miRNA-regulated pathways could contribute to comorbid neurological and cardiovascular disorders will be discussed. Presentation. Changes in miRNA expression occurring in the brain and heart could have an impact on coexisting neurological and cardiovascular characteristics by (1) modulating organ function, (2) accentuating cellular stress, and (3) impinging on neuronal and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in the brain and heart tissues from individuals with comorbid neurodegenerative and cardiovascular disorders will be of great importance and relevance. Implications. Careful experimental design will shed light to the deeper understanding of the molecular mechanisms tying up those different but yet somehow connected diseases.
  • 15.

    【2hr】Matrix Metalloproteinase-9 (MMP9)—A Mediating Enzyme in Cardiovascular Disease, Cancer, and Neuropsychiatric Disorders

    包量

    机译 基质金属蛋白酶9（MMP9）-介导酶在心血管疾病，癌症和神经精神疾病中的作用
    摘要：Matrix metalloproteinase-9 (MMP9) has been implicated in numerous somatic illnesses, including cardiovascular disorders and cancer. Recently, MMP9 has been shown to be increasingly important in several aspects of central nervous system activity. Furthermore, a pathogenic role for this enzyme has been suggested in such neuropsychiatric disorders as schizophrenia, bipolar illness, and multiple sclerosis. In this paper, the results of biochemical and molecular-genetic studies on MMP9 that have been performed in these pathological conditions will be summarized. Furthermore, I hypothesize that the MMP9 gene, as shown by functional −1562 C/T polymorphism studies, may be mediating the relationship of neuropsychiatric illnesses (schizophrenia, bipolar mood disorder, multiple sclerosis) that are comorbid with cardiovascular disease and cancer.
  • 16.

    【2hr】Possible Treatment Concepts for the Levodopa-Related Hyperhomocysteinemia

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    机译 左旋多巴相关高同型半胱氨酸血症的可能治疗概念
    • 作者：Thomas Müller
    • 刊名：Cardiovascular Psychiatry and Neurology
    • 2009年第期
    摘要：The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal—and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.
  • 17.

    【2hr】Role of Hypertension in Aggravating Aβ Neuropathology of AD Type and Tau-Mediated Motor Impairment

    包量

    机译 高血压在加重AD型Aβ神经病理学和Tau介导的运动障碍中的作用
    摘要：Epidemiological evidence suggests that hypertension may accelerate the onset and progression of Alzheimer's disease (AD). In this study, we explored the role of hypertension in the neurodegenerative changes associated with Aβ and tau aggregation. We induced hypertension in APPswe Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-β (Aβ) peptides in brain tissue and a significant reduction of Aβ peptides in serum (P < .05). These results indicate that hypertension may promote AD-type Aβ neuropathology in Tg2576. In P301L-tauTg mice we found that the presence of hypertension was significantly associated with aggravated motor function assessed by hindlimb extension test (P = .01). These results suggest that hypertension may play a role in accelerating the progression of motor dysfunction associated with tau-related alterations. Our studies suggest that the management of blood pressure (BP) may alleviate AD-type Aβ neuropathology and neurological disorders associated with abnormal tau metabolism.
  • 18.

    【2hr】Pharmacological Characterization of Inositol 1,4,5-tris Phosphate Receptors in Human Platelet Membranes

    包量

    机译 人血小板膜中肌醇1,4,5-tris磷酸酯受体的药理特性
    摘要：The phosphatidylinositol (PI) hydrolysis signaling system has been shown to be altered in platelets of depressed and schizophrenic subjects. Inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), an integral component of the PI signaling system, mobilizes Ca2+ by activating Ins(1,4,5)P3 receptors. To eventually investigate the role of Ins(1,4,5)P3 receptors in depression and other mental disorders, we characterized [3H]Ins(1,4,5)P3 binding sites in crude platelet membranes prepared from small amounts of blood obtained from healthy human control subjects. We found a single, saturable binding site for [3H]Ins(1,4,5)P3 to crude platelet membranes, which is time dependent and modulated by pH, inositol phosphates, and heparin. Since cyclic adenosine monophosphate (cAMP) and Ca2+ have been shown to be important modulators in Ins(1,4,5)P3 receptors, in the present study we also determined the effects of various concentrations of CaCI2 and forskolin on Ins(1,4,5)P3 binding to platelet membranes. CaCI2 modulated [3H]Ins(1,4,5)P3 binding sites in a biphasic manner: at lower concentrations it inhibited [3H]Ins(1,4,5)P3 binding, whereas at higher concentrations, it stimulated [3H]Ins(1,4,5)P3 binding. On the other hand, forskolin inhibited [3H]Ins(1,4,5)P3 binding. Our results thus suggest that the pharmacological characteristics of [3H]Ins(1,4,5)P3 binding to crude platelet membranes are similar to that of Ins(1,4,5)P3 receptors; and that both Ca2+ and cAMP modulate [3H]Ins(1,4,5)P3 binding in crude platelet membranes.
  • 19.

    【2hr】The Potential for Xanthine Oxidase Inhibition in the Prevention and Treatment of Cardiovascular and Cerebrovascular Disease

    包量

    机译 黄嘌呤氧化酶抑制在心血管疾病预防和治疗中的潜力
    摘要：There is a now a wealth of epidemiological, animal, and clinical data to suggest the benefits of uric acid reduction and hxanthine oxidase inhibition in prevention of vascular disease. This review discusses the available epidemiological, preclinical, and clinical data and considers arguments for and against a role for serum uric acid in common cardiovascular disorders. It concludes that large scale trials with clinical endpoints are justified to address this important question and to define whether use of drugs such as allopurinol should be a routine part of preventative strategies.
  • 20.

    【2hr】The GRK2 Overexpression Is a Primary Hallmark of Mitochondrial Lesions during Early Alzheimer Disease

    包量

    机译 GRK2过表达是早期阿尔茨海默病期间线粒体病变的主要标志
    摘要：Increasing evidence points to vascular damage as an early contributor to the development of two leading causes of age-associated dementia, namely Alzheimer disease (AD) and AD-like pathology such as stroke. This review focuses on the role of G protein-coupled receptor kinases (GRKs) as they relate to dementia and how the cardio and cerebrovasculature is involved in AD pathogenesis. The exploration of GRKs in AD pathogenesis may help bridge gaps in our understanding of the heart-brain connection in relation to neurovisceral damage and vascular complications of AD. The a priori basis for this inquiry stems from the fact that kinases of this family regulate numerous receptor functions in the brain, myocardium and elsewhere. The aim of this review is to discuss the finding of GRK2 overexpression in the context of early AD pathogenesis. Also, we consider the consequences for this overexpression as a loss of G-protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis through the cerebrovasculature. Finally, we synthesize this newer information in an attempt to put it into context with GRKs as regulators of cellular function, which makes these proteins potential diagnostic and therapeutic targets for future pharmacological intervention.
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