Abstract:
:In the hippocampus, chelatable zinc is accumulated in vesicles of glutamatergic presynaptic terminals, abounding specially in the mossy fibers, from where it is released with activity and can exert a powerful inhibitory action upon N-methyl-D-aspartate receptors. Zinc is therefore in a strategic situation to control overexcitation at the zinc-rich excitatory synapses, and consequently zinc removal during high activity might result in excitotoxic neuronal damage. We analyzed the effect of zinc chelation with sodium dietyldithiocarbamate under overexcitation conditions induced by non-lesioning doses of kainic acid in the mouse hippocampus, to get insight into the role of zinc under overexcitation. Swiss male mice were injected with kainic acid (15 mg/kg, i.p.) 15 min prior to sodium dietyldithiocarbamate (150 mg/kg, i.p.), and left to survive for 6 h, 1 day, 4 days, or 7 days after the treatment. Cell damage was analyzed with the hematoxylin-eosin and acid fuchsin stainings. Neither control animals treated only with kainic acid nor those treated only with sodium dietyldithiocarbamate suffered seizures or neuronal damage. By contrast, the kainic acid+sodium dietyldithiocarbamate-treated animals showed convulsive behavior and cell death involving the hilus, CA3, and CA1 regions. Pretreatment with the N-methyl-D-aspartate receptor antagonist MK801 (1 mg/kg, i.p.) completely prevented neuronal damage. Experiments combining different doses of sodium dietyldithiocarbamate and kainic acid with different administration schedules demonstrated that the overlap of zinc chelation and overexcitation is necessary to trigger the observed effects. Moreover, the treatment with a high dose of sodium dietyldithiocarbamate (1000 mg/kg), which produced a complete bleaching of the Timm staining for approximately 12 h, highly increased the sensitivity of animals to kainic acid. Altogether, our results indicate that the actions of sodium dietyldithiocarbamate are based on a reduction of zinc levels, which under overexcitation conditions induce seizures and neuronal damage. These findings fully support a protective role for synaptically released zinc during high neuronal activity, most probably mediated by its inhibitory actions on N-methyl-D-aspartate receptors, and argue against a direct action of synaptic zinc on the observed neuronal damage.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Domínguez MI,Blasco-Ibáñez JM,Crespo C,Marqués-Marí AI,Martínez-Guijarro FJdoi
10.1016/s0306-4522(02)00731-5keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
791-806issue
3eissn
0306-4522issn
1873-7544pii
S0306452202007315journal_volume
116pub_type
杂志文章相关文献
NEUROSCIENCE文献大全abstract::Dopaminergic mechanisms were analyzed in an isolated preparation of the turtle olfactory bulb. Field potentials were evoked by antidromic or orthodromic stimulation, and the effects determined of pharmacological manipulations of the bathing medium. In the presence of dopamine or a dopamine agonist, apomorphine, there ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(83)90005-2
更新日期:1983-04-01 00:00:00
abstract::Adrenergic modulation of glutamatergic spontaneous miniature excitatory postsynaptic currents (mEPSCs) was investigated in mechanically dissociated rat ventromedial hypothalamic (VMH) neurons using a conventional whole-cell patch clamp technique. Noradrenaline (NA) reversibly increased mEPSC frequency without affectin...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2006.10.049
更新日期:2007-02-23 00:00:00
abstract::It is now well established that vestibular information plays an important role in spatial memory processes. Although vestibular lesions induce anxiety in humans, this finding remains controversial in rodents. However, it is possible that anxiety-related behavior is associated with spatial memory impairments after vest...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2012.05.029
更新日期:2012-08-30 00:00:00
abstract::Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resona...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2013.09.015
更新日期:2013-12-19 00:00:00
abstract::Chronic administration of mu-opioid receptor agonists is known to produce adaptive changes within noradrenergic neurons of the locus coeruleus. Although mu-opioid receptors are densely expressed by locus coeruleus neurons, the effects of acute and chronic administration of agonists on the subcellular distribution of m...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(01)00426-2
更新日期:2001-01-01 00:00:00
abstract::The hippocampus is a multifaceted, complex brain structure considered to be the learning center. The use of primary hippocampal cell cultures has uncovered important cellular mechanisms involved in overall physiological function. Yet, the use of primary culture is inherently difficult, and the lack of immortalized cel...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2010.06.076
更新日期:2010-09-29 00:00:00
abstract::Microglia, the innate immune cells of the brain, regulate brain development through many processes such as synaptic pruning, supporting cell genesis and phagocytosing living and dying cells. There are sex differences in these same developmental processes throughout the brain, thus microglia may contribute to brain sex...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2020.10.009
更新日期:2021-01-15 00:00:00
abstract::Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB(1)) and neuroinflammatory (CB(2)) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how chang...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.01.022
更新日期:2008-03-27 00:00:00
abstract::Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR). The VDR emerges in the rat mesencephalon at embryonic day 12, representing the peak period of dopaminergic cell birth. Our prior studies reveal that developmental...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.07.048
更新日期:2015-09-24 00:00:00
abstract::Updating the position of an earth-fixed target during whole-body rotation seems to rely on cognitive processes such as the utilization of external feedback. According to perceptual learning models, improvement in performance can also occur without external feedback. The aim of this study was to assess spatial updating...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.05.024
更新日期:2015-08-06 00:00:00
abstract::The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2-deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were p...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(90)90200-n
更新日期:1990-01-01 00:00:00
abstract::Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal ser...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(02)00708-x
更新日期:2003-01-01 00:00:00
abstract::Receptor-associated protein appears to play an important role in low-density lipoprotein receptor-related protein trafficking. Since ligands for the low-density lipoprotein receptor-related protein have been implicated in Alzheimer's disease and normal functioning of this protein is indispensable for central nervous s...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00272-3
更新日期:1999-01-01 00:00:00
abstract::In the present study the time-course of DNA fragmentation following insulin-induced hypoglycemia was examined. In situ localization of DNA breaks were studied by the terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labelling method, and the temporal profile of DNA-fragmentation ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(98)00559-4
更新日期:1999-01-01 00:00:00
abstract::Substance P-like immunoreactivity was localized by an indirect immunohistochemical technique in whole mounts and sections of blood vessels from the guinea-pig. There was a widespread association of nerve fibres that had substance P-like immunoreactivity with blood vessels, extending into all vascular beds. The relativ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(82)90279-2
更新日期:1982-02-01 00:00:00
abstract::The present study examined the antihyperalgesic effect of a specific inhibitor of Glycogen Synthase Kinase 3 (GSK3), AR-A014418, on the partial ligation of the sciatic nerve (PSNL), a neuropathic pain model in mice and investigated some mechanisms of action. AR-A014418 (0.01-1 mg/kg) administered by intraperitoneal ro...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2012.09.020
更新日期:2012-12-13 00:00:00
abstract::Clinical and experimental evidence indicates that exposure to alcohol in utero is associated with altered immune capacity. The mechanisms underlying such abnormalities are not clear. However, the suggestion that reciprocal interactions between the immune and the nervous systems are necessary for a competent immune res...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(90)90133-o
更新日期:1990-01-01 00:00:00
abstract::Current theories of neuropathic hypersensitivity include an imbalance of supraspinal inhibition and facilitation. Our overall hypothesis is that the locus coeruleus (LC), classically interpreted as a source of pain inhibition, may paradoxically result in facilitation after tibial and common peroneal nerve transection ...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2009.02.023
更新日期:2009-04-21 00:00:00
abstract::This study shows that the neurons of the entopeduncular nucleus are derived from a longitudinal slab of isochronically generated neurons on day 11 and 15 h of gestation. Many neurons of this longitudinal slab which we have named the basal forebrain cell column, originate from an ependymal matrix closely associated wit...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(86)90032-1
更新日期:1986-03-01 00:00:00
abstract::Astrocytic endothelin receptors are involved in the appearance of activated astrocytes upon injury of the brain [Ishikawa N. et al. (1997) Eur. J. Neurosci. 9, 895-901; Koyama Y. et al. (1999) Glia 26, 268-271]. To clarify signal transduction triggered by endothelin receptors, we examined the effects of endothelins on...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(00)00330-4
更新日期:2000-01-01 00:00:00
abstract::Involvement of both the serotonergic and the endogenous opioid systems in the onset of depressive behavior has been suggested. Previously we showed that serotonin (5-hydroxytryptamine) facilitates beta-endorphin release in the nucleus accumbens (NAcc). Herein, the microdialysis method was used to assess in vivo the ef...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/s0306-4522(01)00612-1
更新日期:2002-01-01 00:00:00
abstract::Intracellular recordings were made from submucous plexus neurons of the guinea-pig cecum maintained in vitro. Histamine (0.3-10 microM) produced a dose-dependent membrane depolarization (congruent to 13 mV with 3 microM) in about 28% of the cells tested; most of these cells showed a prominent calcium-activated potassi...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(89)90018-3
更新日期:1989-01-01 00:00:00
abstract::Retinitis pigmentosa (RP) is a heterogeneous group of retinal degenerative diseases in which the final pathological feature is photoreceptor cell apoptosis. Currently, the pathogenesis of RP remains poorly understood and therapeutics are ineffective. 17β-Oestradiol (βE2) is universally acknowledged as a neuroprotectiv...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2020.11.010
更新日期:2021-01-01 00:00:00
abstract::Neuronal differentiation is a critical developmental process that determines accurate synaptic connection and circuit wiring. A wide variety of naturally occurring compounds have been shown as promising drug leads for the generation and differentiation of neurons. Here we report that a diarylheptanoid from the plant A...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.07.019
更新日期:2015-09-10 00:00:00
abstract::The present studies were undertaken to determine whether the major electrophysiological characteristics of neostriatal neurons are altered during aging. The passive and active membrane properties of 130 neostriatal neurons obtained from young (three to five months, N = 65) and aged (24-26 months, N = 65) Fischer 344 r...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/0306-4522(92)90325-v
更新日期:1992-11-01 00:00:00
abstract::Perineuronal nets of extracellular matrix are associated with distinct types of neurons in the cerebral cortex and many subcortical regions. Large complexes of aggregating proteoglycans form a chemically specified microenvironment around the somata, proximal dendrites and the axon initial segment, including the presyn...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2005.11.068
更新日期:2006-01-01 00:00:00
abstract::To define mechanisms underlying neurovascular injury following brain embolism-induced neurodegeneration, we investigated temporal and spatial pathological changes in brain microvessels up to 12 weeks after microsphere embolism (ME) induction in aged male rats. Mild ME upregulated endothelial nitric oxide synthase (eNO...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.02.044
更新日期:2008-05-02 00:00:00
abstract::Simvastatin is an HMG-CoA reductase inhibitor commonly used in the clinic to treat hypercholesterolemia. In addition, simvastatin has been shown to cross the blood-brain barrier and pleiotropic effects of simvastatin have been reported including anti-inflammatory properties, enhancement of neurite outgrowth, and memor...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2015.02.023
更新日期:2015-04-16 00:00:00
abstract::Fluctuations in the endogenous levels of kynurenic acid (KYNA), a potent alpha7 nicotinic and NMDA receptor antagonist, affect extracellular dopamine (DA) concentrations in the rat brain. Moreover, reductions in KYNA levels increase the vulnerability of striatal neurons to NMDA receptor-mediated excitotoxic insults. W...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2008.11.055
更新日期:2009-03-03 00:00:00
abstract::γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist,...
journal_title:Neuroscience
pub_type: 杂志文章
doi:10.1016/j.neuroscience.2014.07.056
更新日期:2014-09-26 00:00:00