Abstract：
:Complex biological systems are best modeled as highly modular, fluid systems exhibiting a plasticity that allows them to adapt to a vast array of changing conditions. Here we highlight several novel network-based approaches to elucidate genetic networks underlying complex traits. These integrative genomic approaches combine large-scale genotypic and gene expression results in segregating mouse populations to reconstruct reliable genetic networks underlying complex traits such as disease or drug response. We apply these novel approaches to one of the most extensive surveys of gene expression studies ever undertaken in whole brain in a segregating mouse population. More than 23,000 genes were monitored in whole brain samples from more than 300 mice derived from an F2 intercross population and genotyped at over 1200 SNP markers uniformly spread over the entire genome. We explore the topological properties of the brain transcriptional network and highlight different approaches to inferring causal associations among genes by integrating genotypic and expression data. We demonstrate the utility of these approaches by identifying and experimentally validating brain gene expression traits predicted to respond to a strong expression quantitative trait locus (eQTL) for the pituitary tumor-transforming 1 gene (Pttg1) that coincides with the physical location of this gene (a cis eQTL). We identify core functional modules making up the brain transcriptional network in mice that are coherent for core biological processes associated with metabolic disease traits including obesity and diabetes.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Lum PY,Chen Y,Zhu J,Lamb J,Melmed S,Wang S,Drake TA,Lusis AJ,Schadt EEdoi
10.1111/j.1471-4159.2006.03661.xsubject
Has Abstractpub_date
2006-04-01 00:00:00pages
50-62eissn
0022-3042issn
1471-4159pii
JNC3661journal_volume
97 Suppl 1pub_type
杂志文章abstract：:N-Acetyl-L-aspartic acid was identified and determined in human cerebrospinal fluid. The concentration in lumbar fluid was about 2 nmol/ml and about 20 nmol/ml in ventricular fluid. There was no difference between healthy subjects and schizophrenic patients. ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb01208.x
更新日期：1990-05-01 00:00:00
abstract：:The pentameric subunit composition of a large population (36%) of the cerebellar granule cell GABAA receptors that show diazepam (or clonazepam)-insensitive [3H]Ro 15-4513 binding has been determined by immunoprecipitation with subunit-specific antibodies. These receptors have alpha 6, alpha 1, gamma 2S, gamma 2L, and...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63010371.x
更新日期：1994-07-01 00:00:00
abstract：:Presynaptic modulation of synaptic transmission is the primary function of central nicotinic acetylcholine receptors (nAChRs) in developing and adult brain. nAChR activation regulates release of various neurotransmitters, including norepinephrine (NA). Given evidence that NA may serve a critical functional role in cer...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01575.x
更新日期：2003-03-01 00:00:00
abstract：:We have correlated myelin membrane structure with biochemical composition in the CNS and PNS of a phylogenetic series of animals, including elasmobranchs, teleosts, amphibians, and mammals. X-ray diffraction patterns were recorded from freshly dissected, unfixed tissue and used to determine the thicknesses of the liqu...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb08558.x
更新日期：1989-11-01 00:00:00
abstract：:Exposure to cocaine-associated conditioned stimuli elicits craving and increases the probability of cocaine relapse in cocaine users even after extended periods of abstinence. Recent evidence indicates that cocaine seeking can be inhibited by disrupting the reconsolidation of the cocaine cue memories and that basolate...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07277.x
更新日期：2011-07-01 00:00:00
abstract：:Postsynaptic interactions between dopamine and glutamate receptors in the nucleus accumbens are critical for acute responses to drugs of abuse and for neuroadaptations resulting from their chronic administration. We tested the hypothesis that D(1) dopamine receptor stimulation increases phosphorylation of the AMPA rec...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.00877.x
更新日期：2002-06-01 00:00:00
abstract：:The nervous tissue-specific protein B-50 (GAP-43), which has been implicated in the regulation of neurotransmitter release, is a member of a family of atypical calmodulin-binding proteins. To investigate to what extent calmodulin and the interaction between B-50 and calmodulin are involved in the mechanism of Ca(2+)-i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66051933.x
更新日期：1996-05-01 00:00:00
abstract：:The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.62062356.x
更新日期：1994-06-01 00:00:00
abstract：:Using a cell culture model of the blood-brain barrier (BBB), we investigated the brain capillary endothelial cell (EC) response to hypoxia. The activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase and the GSH level of brain capillary ECs alone or i...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65052138.x
更新日期：1995-11-01 00:00:00
abstract：:Frontotemporal lobar degeneration (FTLD) is the second leading cause of dementia in individuals under age 65. In many patients, the predominant pathology includes neuronal cytoplasmic or intranuclear inclusions of ubiquitinated TAR DNA binding protein 43 (FTLD-TDP). Recently, a genome-wide association study identified...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12329
更新日期：2013-09-01 00:00:00
abstract：:Neural progenitor cells isolated from the embryonic cerebral cortex are well known to differentiate into neurons and glial cells, but recent reports have demonstrated differentiation into smooth muscle cells (SMCs) under the influence of fetal bovine serum. In this study, we report that agonists for G protein-coupled ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04405.x
更新日期：2007-05-01 00:00:00
abstract：:To assess the postmortem stability of brain 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) levels, groups of rats and mice were killed by cervical dislocation and left at either 21 degrees or 4 degrees C for intervals of up to 24 h until removal and freezing of whole brain...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1981.tb01679.x
更新日期：1981-03-01 00:00:00
abstract：:In brain, the precursor of imidazoleacetic acid (IAA), a GABAA agonist but a GABAC antagonist, is not known. In the periphery, IAA derives from oxidation of histamine. But in brain, histamine is thought to be metabolized solely by histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele-methylim...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1997.68010142.x
更新日期：1997-01-01 00:00:00
abstract：:We have proposed that a very early step in the pathogenesis of idiopathic Parkinson's disease is the elevated translocation of L-cysteine into neuromelanin-pigmented dopaminergic neurons in the substantia nigra. This influx of L-cysteine was proposed to divert the normal neuromelanin pathway by scavenging dopamine-o-q...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71052049.x
更新日期：1998-11-01 00:00:00
abstract：:Glutamate receptor (GluR) δ1 is widely expressed in the developing forebrain, whereas GluRδ2 is selectively expressed in cerebellar Purkinje cells. Recently, we found that trans-synaptic interaction of postsynaptic GluRδ2 and pre-synaptic neurexins (NRXNs) through cerebellin precursor protein (Cbln) 1 mediates excitat...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2011.07631.x
更新日期：2012-06-01 00:00:00
abstract：:Cyclin-dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre-synaptic terminals triggered by Ca(2+) influx into the pre-synaptic cytoplasm through voltage-dependent Ca(2+) channels (VDCCs). It is reported that Cdk5 regulates L-, P/Q-, or N-type VDCC, but...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12746
更新日期：2014-08-01 00:00:00
abstract：:We examined the effects of cyclic AMP on dopamine receptor-coupled activation of phosphoinositide hydrolysis in rat striatal slices. Forskolin, dibutyryl cyclic AMP, and the protein kinase A activator Sp-cyclic adenosine monophosphothioate (Sp-cAMPS) significantly inhibited inositol phosphate formation stimulated by t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1994.63010222.x
更新日期：1994-07-01 00:00:00
abstract：:The microtubule-based motor protein kinesin is thought to drive anterograde organelle transport in axons, but nothing is known about how its force-generating activity or organelle-binding properties are regulated. Studies in other motility systems suggest that protein phosphorylation is a reasonable candidate for this...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1993.tb03513.x
更新日期：1993-06-01 00:00:00
abstract：:Stabilized microtubules are required for neuronal morphogenesis and migration. However, the underlying mechanism is not fully understood. In this study, we demonstrate that myosin X (Myo10), which is composed of full-length myosin X (fMyo10) and headless myosin X (hMyo10), is important for axon development. fMyo10 is ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.13238
更新日期：2015-10-01 00:00:00
abstract：:Both increased gamma-aminobutyric acid (GABA)-ergic and decreased glutamatergic neurotransmission have been suggested relative to the pathophysiology of hepatic encephalopathy. This proposed disturbance in neurotransmitter balance, however, is based mainly on brain tissue analysis. Because the approach of whole tissue...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1992.tb09410.x
更新日期：1992-08-01 00:00:00
abstract：:The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1-Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched f...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03131.x
更新日期：2005-06-01 00:00:00
abstract：:The in vivo biosynthesis of cholecystokinin (CCK) in subcortical regions of the rat brain was studied by intracisternal pulse injections of [35S]methionine. The rats were killed 1.0 or 1.5 h after the injection. Subcortical CCK extracted in boiling water and acetic acid was immunoabsorbed by an antiserum specific for ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb06290.x
更新日期：1980-08-01 00:00:00
abstract：:This study investigates the functioning of synaptosomal ouabain-sensitive Na+ -K+ -ATPase in cold-induced edema. During vasogenic brain edema development, the enzyme affinities for Na+ and K+ are progressively decreased paralleling the increase in the tissue water content, whereas maximal velocity of the reaction is n...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb09729.x
更新日期：1984-01-01 00:00:00
abstract：:Protein L-isoaspartyl methyltransferase (PIMT) repairs the damaged proteins which have accumulated abnormal aspartyl residues during cell aging. Gene targeting has elucidated a physiological role for PIMT by showing that mice lacking PIMT died prematurely from fatal epileptic seizures. Here we investigated the role of...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2002.01150.x
更新日期：2002-11-01 00:00:00
abstract：:Using ligand binding techniques, we studied beta-adrenergic receptor subtypes in brains obtained at autopsy from seven histologically normal controls and seven histopathologically verified cases with Alzheimer-type dementia (ATD). Inhibition of [3H]dihydroalprenolol [( 3H]DHA) binding by the selective beta 1 antagonis...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05649.x
更新日期：1987-04-01 00:00:00
abstract：:Two monoclonal antibodies that recognize Alzheimer's neurofibrillary tangles (ANTs), AD10 and AB18, have been characterized by immunoblotting against human and calf spinal cord neurofilament (NF) and calf brain microtubule preparations. Both antibodies bind to the 200-kilodalton (kd) (NF-H) and 160-kd (NF-M) but not t...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb04114.x
更新日期：1987-02-01 00:00:00
abstract：:Unilateral frontal cortex ablations were performed in rats so that the glutamate terminals in the ipsilateral rostral neostriatum were removed. At 1 or 7 days later, intraperitoneal injections of ammonium acetate induced different changes in amino acid concentrations in the intact and deafferentated neostriatum. After...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1987.tb05579.x
更新日期：1987-03-01 00:00:00
abstract：:Cocaine- and amphetamine-regulated transcript (CART) is a peptide neurotransmitter that has been implicated in drug reward and reinforcement. CART mRNA and peptide expression are highly concentrated in several compartments of the mesolimbic reward pathway. Several lines of evidence suggest that CART peptides may contr...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03745.x
更新日期：2006-04-01 00:00:00
abstract：:Stressful stimuli induce two distinct cellular reactions, the heat-shock (stress) response and programmed cell death. This study utilizes a dual procedure involving immunocytochemistry for heat-shock protein localization and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2005.03591.x
更新日期：2006-04-01 00:00:00
abstract：:We report on the expression of ionotropic glutamate receptor subunits in primary neuronal cultures from rat cortex, hippocampus and cerebellum and of metabotropic glutamate (mGlu) receptor subtypes in these neuronal cultures as well as in cortical astroglial cultures. We found that the NMDA receptor (NR) subunits NR1,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00369.x
更新日期：2001-06-01 00:00:00
