Search results for "N-methyl-d-aspartate"
showing 10 items of 97 documents
Evidence for an involvement of NMDA and non-NMDA receptors in synaptic excitation of phrenic motoneurons in the rabbit
1991
Abstract The action of endogenous excitatory amino acids on phrenic motoneurons was studied in anesthetized, vagotomized, paralyzed and artificially ventilated rabbits. The NMDA receptor antagonists APV and ketamine, as well as the non-NMDA receptor antagonists GAMS and DNQX were administered by microinjection into the ventral horn of the spinal segments C3-C5. Injection of each antagonist resulted in a reversible reduction of the phrenic nerve activity. Results suggest an important function of endogenous excitatory amino acids in the excitation of phrenic motneurons. NMDA as well as non-NMDA receptors are involved. The functional role of both receptor types in bulbospinal neurotransmission…
Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affi…
2003
The synthetic procedures to obtain indole derivatives with different acidic functions at position 2 of the indole are reported. The synthesised and tested derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2-carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and trifluoromethanesulphonamide moieties. The binding affinity was evaluated using [3H]MDL 105,519 and pig cortical brain membranes. In general, compounds with acidic functions different from a carboxylic acid moiety are less potent than indole-2-carboxylic acid derivatives. Also, the 4,6-dichloro substitution pattern was compared to 5-tert-butyl derivatives and compounds not substituted in the ben…
Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.
2009
N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was ob…
The NMDA receptor complex: a promising target for novel antiepileptic strategies.
2001
Antiepileptic drugs (AEDs) cover a broad spectrum of pathological conditions ranging from seizures following congenital or acquired brain disorders to behavioural and psychiatric disorders and recently neuropathic pain. The need for novel antiepileptics raises from the expanding field of indications as well as from the fact, that special seizure types are refractory to common AEDs. In addition, many of the conventional antiepileptic drugs exhibit an unfavourable side-effect profile. Since there is growing evidence, that NMDA receptor activation might play a crucial role in epilepsy, NMDA receptor antagonists have become compounds of interest in preventing and treating seizures. This review …
Action of anticonvulsants on hippocampal slices in Mg-free medium
1989
The effects of six prototype anticonvulsant drugs were investigated on epileptiform field potential discharges evoked in hippocampal slices of rats by removing magnesium ions from the perfusion fluid in order to reveal a possible interaction with N-methyl-D-aspartate (NMDA) receptor activation. All drugs reduced the multiple discharges with the following order of potency: midazolam greater than carbamazepine = phenytoin = phenobarbital greater than ethosuximide = valproate. They had a stronger depressant effect on the later population spikes but none of them abolished the epileptiform discharge. These effects can be explained by known mechanisms of action of the anticonvulsants tested and l…
Changes in NMDA-receptor function in the first week following laser-induced lesions in rat visual cortex.
2011
Focal brain injuries are accompanied by processes of functional reorganization that partially compensate the functional loss. In a previous study, extracellular recordings at the border of a laser-induced lesion in the visual cortex of rats showed an enhanced synaptic plasticity, which was mediated by the activity of NR2B-contaning NMDA-receptors (NMDARs) shedding light on the potential cellular mechanisms underlying this reorganization. Given the potentially important contribution of NMDARs in processes of functional reorganization, in the present study, we used the same lesion model to further investigate lesion-induced changes in function and localization of NMDARs in the vicinity of the…
The role of N-methyl-D-asparate receptors in neurogenesis.
2006
The dentate gyrus continues to incorporate granule neurons during adulthood. Among the factors that we know modulate adult neurogenesis in the dentate gyrus, one of the first studied was the influence of excitatory amino-acids. These neurotransmitters, acting through NMDA receptors, are able to modulate both the proliferation of progenitor cells as well as the rate of neurogenesis in the adult dentate gyrus. However, the mechanisms by which these processes are influenced are not clearly known. Although there is no anatomical evidence of NMDA receptor expression in adult hippocampal progenitor cells or differentiating granule neurons, electrophysiological data and in vitro studies suggest th…
GABA-A Receptors Regulate Neocortical Neuronal Migration In Vitro and In Vivo
2006
The cortical migration process depends on a number of trophic factors and on the activation of different voltage- and ligand-gated channels. We investigated the role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist muscimol via cortical surface Elvax implants induced prominent alterations in the cortical architecture when compared with untreated or sham-operated controls. BMI- and muscimol-treated animals revealed heterotopic cell clusters in the upper layers and a complete loss of the cortical lamination …
Postsynaptic NO/cGMP Increases NMDA Receptor Currents via Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in the Hippocampus
2013
The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling cascade participates in the modulation of synaptic transmission. The effects of NO are mediated by the NO-sensitive cGMP-forming guanylyl cyclases (NO-GCs), which exist in 2 isoforms with indistinguishable regulatory properties. The lack of long-term potentiation (LTP) in knock-out (KO) mice deficient in either one of the NO-GC isoforms indicates the contribution of both NO-GCs to LTP. Recently, we showed that the NO-GC1 isoform is located presynaptically in glutamatergic neurons and increases the glutamate release via hyperpolarization-activated cyclic nucleotide (HCN)-gated channels in the hippocampus. Electrophysiologi…
Synaptopodin regulates denervation-induced homeostatic synaptic plasticity
2013
Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-de…