Paul J. Lucassen

Bio: Paul J. Lucassen is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Neurogenesis & Hippocampal formation. The author has an hindex of 74, co-authored 254 publications receiving 16424 citations. Previous affiliations of Paul J. Lucassen include University of Bordeaux & Leiden University.

What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated?

Abstract: Even though in vivo imaging studies document significant reductions of hippocampal volume in depressed patients, the exact underlying cellular mechanisms are unclear. Since stressful life events are associated with an increased risk of developing depression, preclinical studies in which animals are exposed to chronic stress have been used to understand the hippocampal shrinkage in depressed patients. Based on morphometrical studies in these models, parameters like dendritic retraction, suppressed adult neurogenesis and neuronal death, all due to elevated levels of glucocorticoids, have been suggested as major causative factors in hippocampal shrinkage. However, histopathological studies examining hippocampi of depressed individuals have so far failed to confirm either a massive neuronal loss or a suppression of dentate neurogenesis, an event that is notably very rare in adult or elderly humans. In fact, many of the structural changes and the volume reduction appear to be reversible. Clearly, more histopathological studies are needed; especially ones that (a) employ stereological quantification, (b) focus on specific cellular elements and populations, and (c) are performed in nonmedicated depressed patients. We conclude that mainly other factors, like alterations in the somatodendritic, axonal, and synaptic components and putative glial changes are most likely to explain the hippocampal shrinkage in depression, while shifts in fluid balance or changes in the extracellular space cannot be excluded either.

Corticotropin-Releasing Hormone mRNA Levels in the Paraventricular Nucleus of Patients With Alzheimer's Disease and Depression

Abstract: Objective: Greater activity of the hypothalamic-pituitary-adrenal (HPA) axis is associated with specific neurological and psychiatric disorders, including Alzheimer’s disease and depression. Hyperactivation ofparaventricular corticotropin-releasing hormone (CRH) neurons may form the basis of this increased activity of the HPA axis. Method: Activation of the CRH neurons was determined through measurement ofthe amount ofCRH-mRNA in the paraventricular nucleus by using quantitative, in situ hybridization histochemistry with systematically sampled frontal sections through the hypothalamus of routinely formalin-fixed and paraffinembedded autopsy brain material of 1 0 comparison subjects, 10 patients with Alzheimer’s disease, and seven depressed patients. Results: CRH-mRNA levels in the paraventricular nucleus ofAlzheimer’s patients were markedly higher than those ofcomparison subjects, whereas CRH-mRNA levels in the paraventricular nucleus ofdepressed patients were even higher than the levels ofAlzheimer’s patients. Conclusions: Paraventricular CRH neurons in Alzheimer’s disease and depression are hyperactivated, and this hyperactivation may contribute to the etiology of these disorders. (AmJ Psychiatry1995; 152:1372-1376)

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

From inflammation to sickness and depression: when the immune system subjugates the brain

Abstract: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

Nitric Oxide and Peroxynitrite in Health and Disease

Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.