Eric J. Nestler

Bio: Eric J. Nestler is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Nucleus accumbens & Ventral tegmental area. The author has an hindex of 178, co-authored 748 publications receiving 116947 citations. Previous affiliations of Eric J. Nestler include University of Maryland, Baltimore & Harvard University.

Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus

Abstract: Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.

The molecular neurobiology of depression

Abstract: Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.

NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

Abstract: Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.

A molecular and cellular theory of depression

Abstract: Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

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。

The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions

Abstract: Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. In addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.