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Resident populations of stem and precursor cells drive the production of new neurons in the adult hippocampus. Recent discoveries have highlighted that a large proportion of these precursor cells are in fact quiescent and can be activated by distinct neuronal activity under both normal physiological and pathological conditions. As growing evidence indicates that newborn neurons play a critical role in cognitive functions such as learning and memory and in mood regulation, it is paramount that we obtain a better understanding of how the reservoirs of stem and precursor cells are maintained and activated. In this review, we critically examine the roles of key molecular mechanisms that have been shown to regulate hippocampal precursor cells, especially their activation. We believe that understanding the mechanistic details of the activity-driven regulation of precursor cells will equip us with the ability to develop tailored strategies to trigger the generation of new neurons, thereby improving the functional outcomes in various neurological and psychiatric conditions. 相似文献
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Alaoui-Ismaili O.; Vernet-Maury E.; Dittmar A.; Delhomme G.; Chanel J. 《Chemical senses》1997,22(3):237-248
The aim of this paper is to analyse the relationship betweenself-report hedonic evaluations and the physiological expressionof emotion in response to odorants. We try to solve the followingquestions: (1) Is it possible to find any experimental evidencethat the sense of smell is linked with emotion? (2) What kindof odorants can be distinguished by autonomic analysis? (3)Is there a link between hedonics and autonomic information?The effects of odorants on the emotional process were estimated,in terms of autonomic nervous system (ANS) activity. Fifteensubjects inhaled five odorants as olfactory stimuli: lavender(LAV), ethyl acetoacetate (EAA), camphor (CAM), acetic acid(AA) and butyric acid (BA). After inhaling the odorant, subjectswere requested to fill out an 11-point hedonic scale to rateits pleasantness versus unpleasantness. ANS parameters wereas follows: two electrodermal responses, skin potential (SP)and resistance (SR); two thermovascular parameters, skin bloodflow (SBF) and skin temperature (ST); and two cardiorespiratoryparameters: instantaneous respiratory frequency (IRF) and instantaneousheart rate (IHR). Simultaneous recording of six parameters showedthat specific autonomic patterns were associated with each odorant.An analysis of variance made it possible to differentiate amongthe five odorants. Two-by-two odorant comparisons for autonomicresponses using Tukey's HSD multiple comparison test only permitteddifferentiation between pleasant odorants (LAV and EAA) andunpleasant (AA and BA) ones, but camphor was differentiatedfrom both pleasant and unpleasant odorants. Each odorant elicitedresponses in the different parameters, yet subjects respondedthrough their preferential channels; an average of two channelswas used by each subject. These results when compared with thoseobtained with other senses (visual and auditory). did not evidencethe postulated preferential link between olfaction and emotion.A'strong link between hedonics and ANS response could be demonstratedwhen considering each subject and mainly through his/her preferentialchannel(s); conversely a weak correlation (SR duration excepted)was obtained between inter-subjects' hedonic evaluation. Itseems that for a given population the autonomic response reflectthe odor valence only through some parameters related to themain preferential channel(s) and thus the global autonomic patternhas to be considered. Chem. Senses 22: 237248, 1997. 相似文献
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New neurons are continuously generated from resident pools of neural stem and precursor cells(NSPCs)in the adult brain.There are multiple pathways through which adult neurogenesis is regulated,and here we review the role of the N-methyl-D-aspartate receptor(NMDAR)in regulating the proliferation of NSPCs in the adult hippocampus.Hippocampal-dependent learning tasks,enriched environments,running,and activity-dependent synaptic plasticity,all potently up-regulate hippocampal NSPC proliferation.We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity,and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons.We address how specific NMDAR agonists and antagonists modulate proliferation,both in vivo and in vitro,and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs.We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis,given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons.In conditions such as age-related memory decline,neurodegeneration and psychiatric disease,mature neurons are lost or become defective;as such,stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions. 相似文献
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Irina N. Krasnova Zuzana Justinova Bruce Ladenheim Subramaniam Jayanthi Michael T. McCoy Chanel Barnes John E. Warner Steven R. Goldberg Jean Lud Cadet 《PloS one》2010,5(1)
Methamphetamine (meth) is an illicit psychostimulant that is abused throughout the world. Repeated passive injections of the drug given in a single day or over a few days cause significant and long-term depletion of dopamine and serotonin in the mammalian brain. Because meth self-administration may better mimic some aspects of human drug-taking behaviors, we examined to what extent this pattern of drug treatment might also result in damage to monoaminergic systems in the brain. Rats were allowed to intravenously self-administer meth (yoked control rats received vehicle) 15 hours per day for 8 days before being euthanized at either 24 hours or at 7 and 14 days after cessation of drug taking. Meth self-administration by the rats was associated with a progressive escalation of daily drug intake to 14 mg/kg per day. Animals that self-administered meth exhibited dose-dependent decreases in striatal dopamine levels during the period of observation. In addition, there were significant reductions in the levels of striatal dopamine transporter and tyrosine hydroxylase proteins. There were also significant decreases in the levels of dopamine, dopamine transporter, and tyrosine hydroxylase in the cortex. In contrast, meth self-administration caused only transient decreases in norepinephrine and serotonin levels in the two brain regions, with these values returning to normal at seven days after cessation of drug taking. Importantly, meth self-administration was associated with significant dose-dependent increases in glial fibrillary acidic protein in both striatum and cortex, with these changes being of greater magnitude in the striatum. These results suggest that meth self-administration by rats is associated with long-term biochemical changes that are reminiscent of those observed in post-mortem brain tissues of chronic meth abusers. 相似文献
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Jér?me Verine Jacqueline Lehmann-Che Hany Soliman Jean-Paul Feugeas Jean-Sébastien Vidal Pierre Mongiat-Artus Stéphanie Belhadj Josette Philippe Matthieu Lesage Evelyne Wittmer Stéphane Chanel Anne Couvelard Sophie Ferlicot Nathalie Rioux-Leclercq Jean-Michel Vignaud Anne Janin Stéphane Germain 《PloS one》2010,5(4)
Background
We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors.Methodology/Principal Findings
Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status.Conclusions/Significance
Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10−49, Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction. 相似文献8.
Verhoog NJ Du Toit A Avenant C Hapgood JP 《The Journal of biological chemistry》2011,286(22):19297-19310
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Fabbri M Smart C Pardi R 《The international journal of biochemistry & cell biology》2003,35(7):1004-1008
T cells are major players in the adaptive immune response to pathogens. They express clonally distributed, highly polymorphic antigen receptors that enable them to recognize cell-associated antigen. Upon antigen recognition, T cells undergo clonal amplification and progressively acquire effector functions, ranging from the production of paracrine soluble factors that provide "help" to other immune cells to the ability to kill pathogen-infected cells with surgical precision. A pool of antigen-reactive T cells reverts to a state of quiescence and maintains a long-lasting memory of antigen encounter. T cells develop in the thymus through a rigorous selection process that recapitulates Darwinian phylogenesis: only the "fittest" survive, i.e. those that can efficiently recognize infectious non-self-antigens but ignore, or are silenced, by non-infectious self-antigens. Due to their ability to discriminate between self and non-self, T cells are the major effectors of allograft rejection. T cells are involved in the pathogenesis of several human disorders, resulting from their defective or dysregulated function. The former leads to a severe state of immunodeficiency, the latter to organ-specific or systemic autoimmunity. 相似文献