Abstract：
:Of the five excitatory amino acid transporters (EAATs) identified, two genes are expressed by neurons (EAAT3 and EAAT4) and give rise to transporters confined to neuronal cell bodies and dendrites. At an ultrastructural level, EAAT3 and EAAT4 proteins are clustered at the edges of postsynaptic densities of excitatory synapses. This pattern of localization suggests that postsynaptic EAATs may help to limit spillover of glutamate from excitatory synapses. In an effort to study transporter localization in living neurons and ultimately to manipulate uptake at intact synapses, we have developed viral reagents encoding neuronal EAATs tagged with GFP. We demonstrate that these fusion proteins are capable of Na(+)-dependent glutamate uptake, that they generate ionic conductances indistinguishable from their wild-type counterparts, and that GFP does not alter their glutamate dose-dependence. Two-photon microscopy was used to examine fusion protein expression in Purkinje neurons in acute cerebellar slices. Both EAAT3-GFP and EAAT4-GFP were observed at high levels in the dendritic spines of transfected Purkinje neurons. These findings indicate that functional EAAT fusion proteins can be synthesized and appropriately trafficked to postsynaptic compartments. Furthermore, they validate a powerful system for looking at EAAT function in situ.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Meera P,Dodson PD,Karakossian MH,Otis TSdoi
10.1016/j.neuropharm.2005.08.015subject
Has Abstractpub_date
2005-11-01 00:00:00pages
883-9issue
6eissn
0028-3908issn
1873-7064pii
S0028-3908(05)00316-3journal_volume
49pub_type
杂志文章abstract：:The activation of Group I metabotropic glutamate receptors (GI mGluRs) in the hippocampus results in the appearance of persistent bursts of synchronised neuronal activity. In response to other stimuli, such activity is known to cause the release of the purines ATP and its neuroactive metabolite, adenosine. We have thu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.01.014
更新日期：2015-06-01 00:00:00
abstract：:The objective of this study was to compare nAChR-mediated neurotransmitter release from slices of rat striatum, frontal cortex and hippocampus following chronic (-)-nicotine (Nic) administration (tartrate salt, 2 mg/kg twice daily for 10 days). Binding studies were also conducted to measure changes in receptor density...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00166-1
更新日期：2002-10-01 00:00:00
abstract：:Receptor-mediated signal transduction is thought to play an important role in neuronal differentiation and the modification of synaptic connections during brain development. The intracellular signalling molecule phospholipase C-beta1 (PLC-beta1), which is activated via specific neurotransmitter receptors, has recently...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00056-2
更新日期：1998-04-01 00:00:00
abstract：:This study was performed to investigate the effects of exercise on the synthesis of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain of the trained rat. The consequences on the relationships between these two systems were also examined. The sum of the levels of free 3,4-dihydroxyphenyl acetic acid (DOPAC) plu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90254-1
更新日期：1987-08-01 00:00:00
abstract：:Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an incre...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.10.040
更新日期：2018-03-15 00:00:00
abstract：:The guinea-pig substantia nigra receives a 5-hydroxytryptaminergic (5-HT ergic) projection from the dorsal raphé nucleus. In this study we have attempted to identify the 5-HT receptor subtype mediating release of acetylcholinesterase (AChE) from nigral neurones, measured by assay of perfusate obtained via chronically ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00088-n
更新日期：1995-09-01 00:00:00
abstract：:Gastrin-releasing peptide (GRP) receptor-expressing (GRPR)+ neurons have a central role in the spinal transmission of itch. Because their fundamental regulatory mechanisms are not yet understood, it is important to determine how such neurons are excited and integrate itch sensation. In this study, we investigated the ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108025
更新日期：2020-06-15 00:00:00
abstract：:In the present study, we studied the interaction between serotonergic (5-HTergic) and gamma-aminobutyric acid (GABA)-ergic systems in the modulation of analgesia from morphine, a mu-opioid agonist, and U50,488, a kappa-opioid agonist. All experiments were performed in mice using the 49 degrees C tail-withdrawal assay....
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00374-x
更新日期：2003-03-01 00:00:00
abstract：:Excitatory neurotransmission mediated by N-methyl-d-aspartate receptors (NMDARs) is fundamental to learning and memory and, when impaired, causes certain neurological disorders. NMDARs are heterotetrameric complexes composed of two GluN1 [NR1] and two GluN2(A-D) [NR2(A-D)] subunits. The GluN2 subunit is responsible fo...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.12.018
更新日期：2012-04-01 00:00:00
abstract：:To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were administered to 6-hydroxydopamine hemilesioned rats, a model of...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108006
更新日期：2020-05-01 00:00:00
abstract：:In Major Depressive Disorder, a growing data base suggests that the onset of antidepressants' action can be detected by improvement of depressive symptoms in the first 10-14 days of treatment. Previous studies showed that the mean concentration of the brain-derived neurotrophic factor (BDNF) in blood increases during ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.07.017
更新日期：2012-01-01 00:00:00
abstract：:Orexins are neuropeptides that are exclusively produced by hypothalamic neurons, which project throughout the entire brain. Orexin, also known as hypocretins, were initially identified to play a fundamental role in food intake, arousal and the regulation of sleep and wakefulness. Recent studies identified orexins to b...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2018.09.034
更新日期：2019-08-01 00:00:00
abstract：:Though amyloid precursor protein (APP) can potentially be cleaved to generate the pathological amyloid β peptide (Aβ), APP itself plays an important role in regulating neuronal activity. APP deficiency causes functional impairment in cholinergic synaptic transmission and cognitive performance. However, the mechanisms ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.08.021
更新日期：2016-11-01 00:00:00
abstract：:Ionic currents from non-inactivating Shaker K(+)-channels were expressed in Xenopus oocytes and recorded with the cut-open oocyte voltage clamp technique. Kinetic properties of ionic currents were studied between 1.4 and 19 degrees C. The forward step of the last transition (...C --> O) of the activation pathway, just...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(96)00111-6
更新日期：1996-01-01 00:00:00
abstract：:Despite notable progress in recent decades, cigarette smoke persists as a leading cause of premature death and preventable disease. To weaken the link between nicotine reinforcement and the toxicity associated with combusted tobacco, the United States Food and Drug Administration is considering a product standard targ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108200
更新日期：2020-09-15 00:00:00
abstract：:The obesity epidemic is one of the biggest health challenges globally and rates have tripled since 1975. Overeating is the largest determinant of obesity, yet little is understood of the neural mechanisms underlying why individuals consume food regardless of satiety. The lateral hypothalamic (LH) input to the ventral ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2019.05.014
更新日期：2019-08-01 00:00:00
abstract：:Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.03.003
更新日期：2017-05-15 00:00:00
abstract：:Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperito...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.10.013
更新日期：2016-02-01 00:00:00
abstract：:More studies are required to develop therapeutic agents for treating spinocerebellar ataxia type 3 (SCA3), which is caused by mutant polyglutamine-expanded ataxin-3 and is the most prevalent subtype of spinocerebellar ataxias. T1-11 [N6-(4-Hydroxybenzyl) adenosine], isolated from a Chinese medicinal herb Gastordia ela...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.08.009
更新日期：2015-12-01 00:00:00
abstract：:A functional balance between excitatory and inhibitory control over dopamine (DA)-dependent behavioral and neurochemical effects of cocaine is afforded by the serotonin(2C) receptor (5-HT(2C)R) located within the ventral tegmental area and the nucleus accumbens (NAc). The 5-HT(2C)R located in the medial prefrontal cor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.10.005
更新日期：2009-02-01 00:00:00
abstract：:Cannabidiol (CBD), a non-euphorigenic compound derived from Cannabis, shows promise for improving recovery following cerebral ischemia and has recently been shown effective for the treatment of childhood seizures caused by Dravet and Lennox-Gastaut syndromes. Given evidence for activity to mitigate effects of CNS insu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.107716
更新日期：2019-11-01 00:00:00
abstract：:Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90077-o
更新日期：1991-06-01 00:00:00
abstract：:Stem cell research offers enormous potential for treating many diseases of the nervous system. At present, therapeutic strategies in stem cell research segregate into two approaches: cell transplantation or endogenous cell stimulation. Realistically, future cell therapies will most likely involve a combination of thes...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2009.10.005
更新日期：2010-05-01 00:00:00
abstract：:Cyclosporine, a calcineurin inhibitor, significantly enhances spontaneous acetylcholine release after a brief tetanus and potentiates the effect of phorbol 12,13-dibutyrate. Both actions are prevented by the protein kinase C inhibitor, bisindolylmaleimide iodide. Protein kinase C and calcineurin thus play important ro...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00178-6
更新日期：1999-01-01 00:00:00
abstract：:Attentional impairments are found in a range of neurodegenerative and neuropsychiatric disorders. However, the development of procognitive enhancers to alleviate these impairments has been hindered by a lack of comprehensive hypotheses regarding the circuitry mediating the targeted attentional functions. Here we discu...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2012.06.060
更新日期：2013-01-01 00:00:00
abstract：:Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters, a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to stress elicit...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.044
更新日期：2016-08-01 00:00:00
abstract：:Thyroid hormone deficiency during early developmental stages causes a multitude of functional and morphological deficits in the brain. In the present study we investigate the effects of a mutated thyroid hormone receptor TR alpha 1 and the resulting receptor-mediated hypothyroidism on the development of GABAergic neur...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.02.005
更新日期：2010-06-01 00:00:00
abstract：:Neurotensin (NTS) is a neuropeptide neurotransmitter expressed in the central and peripheral nervous systems. Many studies over the years have revealed a number of roles for this neuropeptide in body temperature regulation, feeding, analgesia, ethanol sensitivity, psychosis, substance use, and pain. This review provid...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108005
更新日期：2020-05-01 00:00:00
abstract：:Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive imp...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.06.015
更新日期：2017-09-15 00:00:00
abstract：:The effect of KN62 (1-[N,O-bis(5-isoquinolinesulphonyl)-N -methyl-L-tyrosyl]-4-phenylpiperazine), a putative inhibitor of Ca/calmodulin-dependent kinase II (Ca/CaM-K II), on glutamate release from isolated nerve-terminals (synaptosomes) was examined. The drug caused a potent inhibition of KCl- and 4-aminopyridine-evok...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(95)00051-7
更新日期：1995-07-01 00:00:00
