Abstract:
:We report that a subtoxic dose of the succinate dehydrogenase (SDH) inhibitor malonate greatly enhances the neurotoxicity of three different excitatory amino acid agonists: N-methyl-D-aspartate (NMDA), S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA), and L-glutamate. In male Sprague-Dawley rats, intrastriatal stereotaxic injection of malonate alone (0.6 mumol), NMDA alone (15 nmol), S-AMPA alone (1 nmol), or glutamate alone (0.6 mumol) produced negligible toxicity as assessed by measurement of lesion volume. Coinjection of subtoxic malonate with NMDA produced a large lesion (15.2 +/- 1.4 mm3), as did coinjection of malonate with S-AMPA (11.0 +/- 1.0 mm3) or glutamate (12.8 +/- 0.7 mm3). Administration of the noncompetitive NMDA antagonist MK-801 (5 mg/kg i.p.) completely blocked the toxicity of malonate plus NMDA (0.5 +/- 0.3 mm3). This dose of MK-801 had little effect on the lesion produced by malonate plus S-AMPA (9.0 +/- 0.7 mm3), but it attenuated the toxicity of malonate plus glutamate by approximately 40% (7.5 +/- 0.9 mm3). Coinjection of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBQX; 2 nmol) had no effect on malonate plus NMDA or malonate plus glutamate toxicity (12.3 +/- 1.8 and 14.0 +/- 0.9 mm3, respectively) but greatly attenuated malonate plus S-AMPA toxicity (1.5 +/- 0.9 mm3). Combination of the two antagonists conferred no additional neuroprotection in any paradigm. These results indicate that metabolic inhibition exacerbates both NMDA receptor- and non-NMDA receptor-mediated excitotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Greene JG,Greenamyre JTdoi
10.1046/j.1471-4159.1995.64052332.xsubject
Has Abstractpub_date
1995-05-01 00:00:00pages
2332-8issue
5eissn
0022-3042issn
1471-4159journal_volume
64pub_type
杂志文章abstract::Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kin...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2005.03553.x
更新日期:2006-01-01 00:00:00
abstract::A rapid loss of protein kinase C (PKC) activity is a prognostic feature of the lethal damage inflicted on neurons by cerebral ischemia in vivo and by hypoxic and excitotoxic insults in vitro. However, it is not known if this inactivation of PKC is incidental or is an essential part of the neurodegenerative process dri...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1997.68041400.x
更新日期:1997-04-01 00:00:00
abstract::These studies were undertaken to test the hypothesis that alterations in phosphatidylinositol metabolism can modulate neurotransmitter release in the central nervous system. The effects of 1,2-diacylglycerols (DAGs) on dopamine release in the rat central nervous system were determined by measuring dopamine release fro...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb01922.x
更新日期:1990-02-01 00:00:00
abstract::A combination of posttranslational modifications contributes to the high heterogeneity of brain tubulin in mammals. In this report, the structures of the detyrosinated carboxy-terminal peptides of alpha-tubulin from newborn and adult mouse brain were compared. The heterogeneity of these carboxy-terminal peptides was o...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67052104.x
更新日期:1996-11-01 00:00:00
abstract::The extracellular concentrations of amino acids in the hippocampal CA1 field and striatum of conscious freely moving rats were monitored simultaneously by in vivo brain microdialysis using HPLC with electrochemical detection. Under basal conditions, aspartate, glutamate, glutamine, glycine, taurine, and alanine were d...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1993.tb09806.x
更新日期:1993-11-01 00:00:00
abstract::Proper brain function in the nervous system relies on the accurate establishment of synaptic contacts during development. Countless synapses populate the adult brain in an orderly fashion. In each synapse, a presynaptic terminal loaded with neurotransmitters-containing synaptic vesicles is perfectly aligned to an arra...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/jnc.13702
更新日期:2016-12-01 00:00:00
abstract::Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substu...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1471-4159.2012.07683.x
更新日期:2012-04-01 00:00:00
abstract::We have examined the binding of the adenosine agonist radioligands [3N]N6-cyclohexyladenosine ([3H]CHA) and [3H]5'-N-ethylcarboxamidoadenosine ([3H]NECA) to membranes prepared from postmortem human pineal glands. The results showed that the A-1-specific ligand CHA did not bind to membranes. By contrast, [3H]NECA, a no...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1990.tb03141.x
更新日期:1990-10-01 00:00:00
abstract::45Ca2+ uptake measurements were performed on intact and osmotically lysed synaptosomes from rat brain to study the possible influence of prostaglandins (PGs) on Ca2+ movements into and within the nerve endings. The K+-induced 45Ca2+ uptake of intact synaptosomes was not influenced by several inhibitors of PG synthesis...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb03972.x
更新日期:1982-08-01 00:00:00
abstract::Several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson's disease (PD). Using enantiomeric-selective high-performance liquid chromatography with electrochem...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2008.05709.x
更新日期:2008-12-01 00:00:00
abstract::Superfusion of striatal slices with a medium deficient in Ca2+ and Mg2+ caused a large and sustained increase in release of lactate dehydrogenase, a finding indicative of the disruption of plasma membranes. This was associated with an efflux of dopamine (DA) and the depletion of DA from the tissue. In addition, wherea...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb11445.x
更新日期:1991-04-01 00:00:00
abstract::Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) have been implicated in membrane-cytoskeletal events underlying cell adhesion, migration, secretion, and phagocytosis. In BV-2 microglial cells, lipopolysaccharide (LPS) elicited a dose-dependent increase in mRNA of both MRP (sixfo...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.2001.00458.x
更新日期:2001-08-01 00:00:00
abstract::Injury-induced cytokines act through gp130 in sympathetic neurons to suppress expression of tyrosine hydroxylase (TH) and other genes associated with noradrenergic transmission. These cytokines also trigger the local loss of TH in peri-infarct sympathetic axons after myocardial infarction, but altered gene expression ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07539.x
更新日期:2012-01-01 00:00:00
abstract::Choline acetyltransferase activity is barely detectable in a mutant pheochromocytoma PC12 cell line, A123.7, which is deficient in protein kinase A activity. Northern blot and polymerase chain reaction analyses showed that this mutant cell line has dramatically reduced levels of choline acetyltransferase mRNA, which c...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1995.64030985.x
更新日期:1995-03-01 00:00:00
abstract::Apolipoprotein E (apoE) plays a crucial role in lipid transport in circulation and the brain. The apoE4 isoform is a major risk factor for Alzheimer's disease (AD). ApoE4 is more susceptible to proteolysis than other apoE isoforms and apoE4 fragments have been found in brains of AD patients. These apoE4 fragments have...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2010.06756.x
更新日期:2010-11-01 00:00:00
abstract::The I1-imidazoline receptor (I1R) is a proposed target for drug action relevant to blood pressure and glucose control. The imidazoline receptor antisera-selected (IRAS) gene, also known as Nischarin, has several characteristics of an I1R. To test the contribution of IRAS to I1R binding capacity and cell-signaling func...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2006.04413.x
更新日期:2007-04-01 00:00:00
abstract::Neuromodulation is a fundamental process in the brain that regulates synaptic transmission, neuronal network activity and behavior. Emerging evidence demonstrates that astrocytes, a major population of glial cells in the brain, play previously unrecognized functions in neuronal modulation. Astrocytes can detect the le...
journal_title:Journal of neurochemistry
pub_type: 杂志文章,评审
doi:10.1111/j.1471-4159.2008.05830.x
更新日期:2009-02-01 00:00:00
abstract::Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with in...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13347
更新日期:2015-12-01 00:00:00
abstract::Terminally differentiated PC12 cells are a useful neuron-like model for studying programmed cell death in response to nerve growth factor (NGF) deprivation. This in vitro model was used to investigate the mechanism by which cyanide-induced histotoxic hypoxia produces neuronal degeneration. Treatment of undifferentiate...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.67031039.x
更新日期:1996-09-01 00:00:00
abstract::The metabolism of the positron-emitting compound [18F]6-fluoro-L-3,4-dihydroxyphenylalanine (*F-DOPA) was studied in carbidopa-pretreated male hooded rats. Thirty minutes following carbidopa administration (5 mg/kg i.p.), animals received *F-DOPA (500 micrograms/kg; specific activity, 175-230 Ci/mol) as an intrajugula...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1987.tb04135.x
更新日期:1987-02-01 00:00:00
abstract::The levels of mRNA encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE) were measured by Northern blot analysis, in the dorsal and the ventral part of the striatum, following long-term treatments with drugs acting selectively on D1 or D2 dopaminergic receptors. Chronic injection of the selective D1 an...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb08168.x
更新日期:1991-02-01 00:00:00
abstract::Steroidogenic acute regulatory protein (StAR) is a 30-kDa protein involved in the transport of cholesterol to the inner mitochondrial membrane and thus plays a key role in steroid biosynthesis. To clarify the implications of this protein in neurosteroid biosynthesis, we examined the possible expression of a StAR trans...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1998.71062231.x
更新日期:1998-12-01 00:00:00
abstract::The question of developmental relationships amongst myelin-related membranes in subfractions of myelinating mouse brain (15 days) was investigated by a time-staggered double isotope protocol using [3H]leucine and [14C]leucine. Preliminary results are interpreted and discussed in the context of a mathematical conceptua...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1983.tb09041.x
更新日期:1983-10-01 00:00:00
abstract::Gs alpha, the GTP-binding protein that mediates receptor stimulation of adenylyl cyclase, exists in small (Gs alpha-S) and large (Gs alpha-L) molecular forms. Previous work has established that these Gs alpha isoforms are products of alternatively spliced Gs alpha pre-mRNA. The present work examined the splicing patte...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1991.tb08252.x
更新日期:1991-09-01 00:00:00
abstract::Several epidemiological and preclinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), reduce the risk of Alzheimer's disease (AD) and can lower β-amyloid (Aβ) production and inhibit neuroinflammation. However, follow-up clinical trials, mostly using selective ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.12059
更新日期:2013-01-01 00:00:00
abstract::In the present study, the properties, such as pH optima, detergent requirement, and effects of various lipids, of cholesterol ester hydrolase in human cerebrospinal fluid (CSF) were examined, and the activity levels of the enzyme in CSF from multiple sclerosis (MS) patients and non-MS individuals were compared. Our da...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.1982.tb12527.x
更新日期:1981-09-01 00:00:00
abstract::Recent evidence indicates that supplementation with a specific combination of nutrients may affect cell membrane synthesis and composition. To investigate whether such nutrients may also modify the physical properties of membranes, and affect membrane-bound processes involved in signal transduction pathways, we studie...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/j.1471-4159.2011.07616.x
更新日期:2012-02-01 00:00:00
abstract::Endocannabinoids (eCB) are key regulators of excitatory/inhibitory neurotransmission at cannabinoid-1-receptor (CB1 R)-expressing axon terminals. The most abundant eCB in the brain, that is 2-arachidonoylglycerol (2-AG), is hydrolyzed by the enzyme monoacylglycerol lipase (MAGL), whose chronic inhibition in the brain ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1111/jnc.13267
更新日期:2015-11-01 00:00:00
abstract::The Na(+)-glutamate cotransporters are believed to countertransport OH- and K+. Previous evidence that the velocity of glutamate uptake can exceed the acid extrusion capacity of astrocytes raised the question of whether intracellular pH can become rate limiting for glutamate uptake. Cytoplasmic buffering capacity and ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1996.66010169.x
更新日期:1996-01-01 00:00:00
abstract::The murine neuroblastoma N1E-115 cell line possesses a high density of angiotensin II (AngII) receptors that can be solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. These solubilized binding sites exhibited high affinity for CGP-42112A and not Losartan, indicating ...
journal_title:Journal of neurochemistry
pub_type: 杂志文章
doi:10.1046/j.1471-4159.1994.62062106.x
更新日期:1994-06-01 00:00:00