Abstract：
:NMDA receptors are essential for neurotransmission and key mediators of synaptic signaling, but they can also trigger deleterious degenerative processes that lead to cell death. Growing evidence suggests that selective blockade of the heterogeneous subunits that comprise the NMDA receptor may enable better control of pharmacotherapies for treating neurological diseases and injuries. We investigated the relationship between NMDAR activation, MAPK signaling, and mitochondrial shape following an excitotoxic insult. NR2A- and NR2B-containing NMDARs differentially mediated acute changes in cytosolic calcium, alterations in mitochondrial morphology, and phosphorylation of the MAPKs ERK and JNK. Activation of NR2A-containing NMDARs was associated with JNK phosphorylation that was neuroprotective in neuronal cultures subjected to excitotoxicity. In contrast, activation of NR2B-containing NMDARs triggered calcium accumulation in mitochondria that was strongly associated with mitochondrial swelling and neuronal cell death. Indeed, while blockade of NR2B-containing receptors was neuroprotective, this protection was lost when NR2A-initiated JNK phosphorylation was inhibited. Given the modest selectivity of the NR2A inhibitor, NVP-AAM077, the results highlight the significance of the relative, rather than absolute, activation of these two NMDA subtypes in modulating cell death pathways. Therefore, the balance between concurrent activation of NR2B-containing and NR2A-containing NMDARs dictates neuronal fate following excitotoxicity.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Choo AM,Geddes-Klein DM,Hockenberry A,Scarsella D,Mesfin MN,Singh P,Patel TP,Meaney DFdoi
10.1016/j.neuint.2012.02.007subject
Has Abstractpub_date
2012-04-01 00:00:00pages
506-16issue
5eissn
0197-0186issn
1872-9754pii
S0197-0186(12)00058-7journal_volume
60pub_type
杂志文章abstract：:Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of diabetes patients, however, the neural mechanisms underlying DNP remain unclear. Endomorphins are the endogenous ligands for mu-opioid receptor. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neur...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2017.05.014
更新日期：2017-09-01 00:00:00
abstract：:Carotenoids play a pivotal role in prevention of many degenerative diseases mediated by oxidative stress including neurodegenerative diseases like Alzheimer's Disease (AD). The involvement of retinoids in physiology, AD pathology and their therapeutic role in vitro and in vivo has been extensively studied. This review...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2011.04.004
更新日期：2011-10-01 00:00:00
abstract：:Microglial activation has been implicated in neurodegenerative diseases. Therefore, inhibition of inflammation mediated by microglia is a strategy in neurodegenerative disease therapy. In this study, we isolated cryptotanshinone and 15,16-dihydrotanshinone I from Salvia miltiorrhiza, a traditional Korean herb medicine...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2005.07.004
更新日期：2006-01-01 00:00:00
abstract：:To investigate the contribution of the dopamine (DA) synthesis to both the calcium-dependent and the carrier-mediated, mechanisms of DA release in the striatum, anaesthetized rats were locally superfused in the striatum with a push pull cannula supplied with an artificial CSF containing tritiated tyrosine. DA, dihydro...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(99)00094-7
更新日期：1999-12-01 00:00:00
abstract：:The function of PMP70, one of the four ABC half-transporters of mammalian peroxisomes, encoded by ABCD3 gene, is still unclear. The finding that PMP70 over-expression partially corrected very long-chain fatty acid oxidation defects in fibroblasts of X-linked adrenoleukodystrophy patients, has unveiled its potential cl...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2007.11.007
更新日期：2008-05-01 00:00:00
abstract：:Homozygous deletion or mutation in the survival motor neuron (SMN)1 gene causes proximal spinal muscular atrophy (SMA), whereas SMN2 acts as a modifying gene that can influence the severity of SMA. It has been suggested that restoration of the SMN protein level in neuronal cells may prevent cell loss and may be helpfu...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2004.04.005
更新日期：2004-12-01 00:00:00
abstract：:Astrocytes play an important role in chemical signalling, acting as receptive as well as secretory elements. They can express receptors for essentially all classical neurotransmitter substances and for a large variety of peptides. Recent evidence indicates that astrocytes are involved in the information processing wit...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/s0197-0186(02)00045-1
更新日期：2002-11-01 00:00:00
abstract：:The phosphorylation of proteins on tyrosine residues, initially believed to be primarily involved in cell growth and differentiation, is now recognized as having a critical role in regulating the function of mature cells. The brain exhibits one of the highest levels of tyrosine kinase activity in the adult animal and ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/s0197-0186(97)00022-3
更新日期：1997-11-01 00:00:00
abstract：:Neuroblastoma cells, cultivated on plastic dishes, in presence of 15 mM glucose resist very well to hypoxia. Cells incubated on plastic dishes, if left unshaken, showed a Pasteur effect at an oxygen concentration below 10%. Oxygen diffusion was the limiting factor in these plastic dishes since improved oxygen diffusio...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(84)90116-5
更新日期：1984-01-01 00:00:00
abstract：:Serotonin2C receptor (5-HT2C) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT2C receptor agonist WAY-163909 (0.3 and 3 ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.01.019
更新日期：2019-03-01 00:00:00
abstract：:Hydrogen sulfide (H(2)S) is a novel neurotransmitter. We studied here the effect of ACS 84, a new H(2)S releasing compound, on the cytotoxicity induced by amyloid beta (Aβ) in microglia. Treatment with Aβ(1-40) (25μmol/L) for 24h significantly inhibited MTT reduction and increased lactate dehydrogenase release in BV-2...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2011.01.023
更新日期：2011-04-01 00:00:00
abstract：:Platelet-activating factor (PAF), a biologically active lipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoholine), is identified in different regions of brain, including hippocampus. Specific PAF-activated receptors (PAFRs) are expressed in corresponding brain areas. PAF has been proposed to be a retrograde messenger of l...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(03)00126-8
更新日期：2004-02-01 00:00:00
abstract：:Streptozotocin (STZ) is a glucosamine-nitrosourea commonly used to induce long-lasting models of diabetes mellitus and Alzheimer's disease. Direct toxicity of STZ on the pancreas and kidneys has been well characterized, but the acute effect of this compound on brain tissue has received less attention. Herein, we inves...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2019.04.013
更新日期：2019-09-01 00:00:00
abstract：:Mecamylamine is a well-described non specific antagonist of nicotinic acetylcholine receptors (nAChRs), used in therapy and in psychopharmacological studies. [(11)C]-Mecamylamine was prepared and evaluated as a putative radioligand for positron emission tomography to study nicotinic acetylcholine receptors. The radios...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2004.12.003
更新日期：2005-05-01 00:00:00
abstract：:Brain cortex synaptoneurosomes actively incorporated [14C]arachidonic acid (AA) into lipids. Serotonin (5-HT), at a concentration range of 10 microM-1 mM, significantly stimulates the incorporation of AA mainly into phosphatidylinositol (PI) of brain cortex synaptoneurosomes. The stimulation rate of AA incorporation b...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(94)90039-6
更新日期：1994-08-01 00:00:00
abstract：:The neonatal administration of 5,7-dihydroxytryptamine to rats (100 mg kg(?1) s.c. on the 1st and 2nd day after birth) resulted in marked reductions in serotoninergic presynaptic markers ([(3)H]-5-HT synaptosomal uptake, tryptophan hydroxylase activity and endogenous 5-HT content) in various forebrain areas, particula...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(81)90051-6
更新日期：1981-03-01 00:00:00
abstract：:Oxidative stress has for long been linked to the neuronal cell death in many neurodegenerative conditions. Conventional antioxidant therapies have been less effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Nanoparticle antioxidants constitute a...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2015.08.011
更新日期：2015-10-01 00:00:00
abstract：:There is a growing body of evidence on the role of nitric oxide (NO) in retinal physiology. Recently, interest has developed in the functional role of an alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed by a number of diverse biochemical reactions. The aim of the present report was to co...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2007.04.015
更新日期：2007-11-01 00:00:00
abstract：:Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2014.07.007
更新日期：2014-12-01 00:00:00
abstract：:Taurine is found at millimolar concentration in the retina and retinal pigment epithelium. High concentrations of taurine are essential for maintenance of retinal function. Taurine uptake by retina and retinal pigment epithelium was significantly enhanced by physiological concentrations of insulin as well as by high g...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(99)00072-8
更新日期：1999-10-01 00:00:00
abstract：:The iron siderophore binding protein lipocalin 2 (LCN2, also known as 24p3, NGAL and siderocalin) may be involved in iron homeostasis, but to date, little is known about expression of its putative receptor, brain-type organic cation transporter (BOCT, also known as BOCT1, 24p3R, NGALR and LCN2R), in the brain during n...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2015.04.009
更新日期：2015-08-01 00:00:00
abstract：:The discovery of nonsynaptic communication in the 1960s and 1970s was an important milestone in investigating the function of the nervous system, and it revolutionized our view about information transmission between neurons. In addition, nonsynaptic communication has a practical importance not only within the nervous ...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2007.06.001
更新日期：2008-01-01 00:00:00
abstract：:Amiloride, a potassium sparing diuretic, inhibits adenosine A1 receptor-radioligand binding in calf and rat brain membranes in the low micromolar range. The drug interacted with the A1 receptor in a manner different from classical A1 ligands, but structure-activity relationship studies indicated that this inhibitory e...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(92)90169-r
更新日期：1992-02-01 00:00:00
abstract：:Astroglial cells have a variety of roles in the central nervous system (CNS), providing a homeostasis for the proper functioning of neuronal cells. The classical view concerning the supportive role of astroglia towards associated neurons has to be extended. A great number of new evidences suggest that astrocytes inter...
journal_title：Neurochemistry international
pub_type： 杂志文章,评审
doi：10.1016/j.neuint.2009.01.025
更新日期：2009-07-01 00:00:00
abstract：:Oxidative stress-induced neuronal death due to hydrogen peroxide overload plays a critical role in the pathogenesis of numerous neurological diseases. Insulin-like growth factor-1 (IGF-1) is important in maintaining neuronal survival, proliferation, and differentiation in the central nervous system. We now report that...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2007.04.005
更新日期：2007-11-01 00:00:00
abstract：:Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain, has been shown to be up-regulated in Alzheimer's disease (AD). Inhibition of tPA activity leads to reduced brain levels of plasmin, one of the main enzymes responsible for the degradation and clearance of amyloid-beta and its plaques from...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2013.08.010
更新日期：2013-11-01 00:00:00
abstract：:The present experiments investigated the effect of a neurotoxin purified from the venom of the spider Phoneutria nigriventer. This toxic component, P. nigriventer toxin 3-6 (PnTx3-6), abolished Ca(2+)-dependent glutamate release with an IC(50) of 74.4nM but did not alter Ca(2+)-independent secretion of glutamate when ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(02)00130-4
更新日期：2003-03-01 00:00:00
abstract：:Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) wi...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/j.neuint.2009.10.001
更新日期：2010-01-01 00:00:00
abstract：:The purpose of this study was to investigate the effect of (3S)-7-chloro-3-[2-((1R)-1-carboxyethoxy)-4-aminomethylphenyl]aminocarbonylmethyl-1,3,4,5-tetrahydrobenz[c,d]indole-2-carboxylic acid hydrochloride (SM-31900), an antagonist with high selectivity and affinity for the NMDA receptor glycine-binding site, on the ...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/s0197-0186(02)00137-7
更新日期：2003-04-01 00:00:00
abstract：:We demonstrated that genetically modified fibroblasts can be encapsulated into biocompatible, biodegradable spheres retaining their viability and capacity to continuously secrete nerve growth factor (NGF) for at least two months. Genetically engineered rat fibroblasts producing NGF were encapsulated in an alginate-pol...
journal_title：Neurochemistry international
pub_type： 杂志文章
doi：10.1016/0197-0186(93)90089-n
更新日期：1993-08-01 00:00:00
