Abstract:
:Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transporter Eaat1 is observed in these animals, leading to reduced uptake of glutamate by astrocytes. As a consequence, glutamate levels increase in the extracellular space of Per2(Brdm1) mutant mouse brains. This is accompanied by increased alcohol intake in these animals. In humans, variations of the PER2 gene are associated with regulation of alcohol consumption. Acamprosate, a drug used to prevent craving and relapse in alcoholic patients is thought to act by dampening a hyper-glutamatergic state. This drug reduced augmented glutamate levels and normalized increased alcohol consumption in Per2(Brdm1) mutant mice. Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake.
journal_name
Nat Medjournal_title
Nature medicineauthors
Spanagel R,Pendyala G,Abarca C,Zghoul T,Sanchis-Segura C,Magnone MC,Lascorz J,Depner M,Holzberg D,Soyka M,Schreiber S,Matsuda F,Lathrop M,Schumann G,Albrecht Udoi
10.1038/nm1163keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
35-42issue
1eissn
1078-8956issn
1546-170Xpii
nm1163journal_volume
11pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0323-0
更新日期:2019-03-01 00:00:00
abstract::Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3695
更新日期:2014-11-01 00:00:00
abstract::Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that rates of mitochondria...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3415
更新日期:2014-01-01 00:00:00
abstract::Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0298-235
更新日期:1998-02-01 00:00:00
abstract::New technology has provided methods for collecting large amounts of data reflecting gene expression, metabolite and protein abundance, and post-translational modification of proteins. Integration of these various data sets enable the genetic mapping of many new phenotypes and facilitates the creation of network models...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0410-388
更新日期:2010-04-01 00:00:00
abstract::Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/84643
更新日期:2001-02-01 00:00:00
abstract::While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a regi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/91008
更新日期:2001-08-01 00:00:00
abstract::Relapse is the leading cause of mortality in children with acute lymphoblastic leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL combination therapy. Using whole-exome sequencing, we identified relapse-specific mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encod...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3840
更新日期:2015-06-01 00:00:00
abstract::We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent ap...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1127
更新日期:2004-11-01 00:00:00
abstract::Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apopto...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1403
更新日期:2006-06-01 00:00:00
abstract::A new investigation into Duchenne muscular dystrophy (DMD) pathogenesis suggests that at least part of the muscle degeneration observed in DMD patients may result from the reduced production of muscle membrane-associated neuronal nitric oxide synthase. This reduction may lead to impaired regulation of the vasoconstric...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/83309
更新日期:2001-01-01 00:00:00
abstract::Hereditary hemochromatosis and transfusional iron overload are frequent clinical conditions associated with progressive iron accumulation in parenchymal tissues, leading to eventual organ failure. We have discovered a new mechanism to reverse iron overload-pharmacological modulation of the divalent metal transporter-1...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1542
更新日期:2007-04-01 00:00:00
abstract::Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1693
更新日期:2008-01-01 00:00:00
abstract::The mechanism by which angiogenic factors recruit bone marrow (BM)-derived quiescent endothelial and hematopoietic stem cells (HSCs) is not known. Here, we report that functional vascular endothelial growth factor receptor-1 (VEGFR1) is expressed on human CD34(+) and mouse Lin(-)Sca-1(+)c-Kit(+) BM-repopulating stem c...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm740
更新日期:2002-08-01 00:00:00
abstract::The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation st...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm961
更新日期:2003-12-01 00:00:00
abstract::Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-deri...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3516
更新日期:2014-05-01 00:00:00
abstract::The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essenti...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/81380
更新日期:2000-11-01 00:00:00
abstract::CD4(+) T cells that express the forkhead box P3 (FOXP3) transcription factor function as regulatory T (Treg) cells and hinder effective immune responses against cancer cells. Abundant Treg cell infiltration into tumors is associated with poor clinical outcomes in various types of cancers. However, the role of Treg cel...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4086
更新日期:2016-06-01 00:00:00
abstract::Two big challenges of transplantation biology are controlling the reaction of the graft to the host after hematopoietic stem cell transplantation and preventing rejection of donor organs by the host. Raewyn Broady and Megan K. Levings discuss the first challenge, examining studies suggesting that statins might be help...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1108-1155
更新日期:2008-11-01 00:00:00
abstract::Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0596-529
更新日期:1996-05-01 00:00:00
abstract::The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm859
更新日期:2003-05-01 00:00:00
abstract::Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of generating and maintaining lifelong the extremely diverse pool of blood cells1. Clinically, transplantation of human HSPC from an allogeneic healthy donor or infusion of autologous gene-corrected HSPC can effectively replenish defective blood ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0195-3
更新日期:2018-11-01 00:00:00
abstract::The cycle of gallbladder filling and emptying controls the flow of bile into the intestine for digestion. Here we show that fibroblast growth factor-15, a hormone made by the distal small intestine in response to bile acids, is required for gallbladder filling. These studies demonstrate that gallbladder filling is act...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1501
更新日期:2006-11-01 00:00:00
abstract::Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a,...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1570
更新日期:2007-05-01 00:00:00
abstract::A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene ex...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/2042
更新日期:1998-09-01 00:00:00
abstract::Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/86507
更新日期:2001-04-01 00:00:00
abstract::Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how t...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4238
更新日期:2016-12-06 00:00:00
abstract::One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/78682
更新日期:2000-08-01 00:00:00
abstract::Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemic...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1026
更新日期:2004-05-01 00:00:00
abstract::The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and me...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1735
更新日期:2008-05-01 00:00:00