Search results for "Kainate receptor"
showing 10 items of 27 documents
Encephalitis with Autoantibodies against the Glutamate Kainate Receptors GluK2
2021
OBJECTIVE: The objective of this study was to report the identification of antibodies against the glutamate kainate receptor subunit 2 (GluK2-abs) in patients with autoimmune encephalitis, and describe the clinical-immunological features and antibody effects. METHODS: Two sera from 8 patients with similar rat brain immunostaining were used to precipitate the antigen from neuronal cultures. A cell-based assay (CBA) with GluK2-expressing HEK293 cells was used to assess 596 patients with different neurological disorders, and 23 healthy controls. GluK2-ab effects were determined by confocal microscopy in cultured neurons and electrophysiology in GluK2-expressing HEK293 cells. RESULTS: Patients'…
Reverse screening on indicaxanthin from Opuntia ficus-indica as natural chemoactive and chemopreventive agent
2018
Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydr…
Glutamate Activates Phospholipase D in Hippocampal Slices of Newborn and Adult Rats
1993
Phospholipase D (PLD) is activated by many neurotransmitters in a novel signal transduction pathway. In the present work, PLD activity was studied comparatively in hippocampal slices of newborn and adult rats. Basal PLD activity in adult rats was almost three times higher than in newborn rats. In newborn rats, L-glutamate and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) time- and concentration-dependently enhanced the formation of [3H]phosphatidylpropanol ([3H]PP) and of [3H]phosphatidic acid in the presence of 2% propanol. N-Methyl-D-aspartate and kainate (both 1 mM) caused small, but significant increases (approximately 50%), whereas alpha-amino-3-hydroxy-5-methylisoxazole…
Exploring kainate receptor pharmacology using molecular dynamics simulations.
2010
Ionotropic glutamate receptors (iGluRs) are enticing targets for pharmaceutical research; however, the search for selective ligands is a laborious experimental process. Here we introduce a purely computational procedure as an approach to evaluate ligand–iGluR pharmacology. The ligands are docked into the closed ligand-binding domain and during the molecular dynamics (MD) simulation the bi-lobed interface either opens (partial agonist/antagonist) or stays closed (agonist) according to the properties of the ligand. The procedure is tested with closely related set of analogs of the marine toxin dysiherbaine bound to GluK1 kainate receptor. The modeling is set against the abundant binding data …
Carbachol-induced network oscillations in the intact cerebral cortex of the newborn rat.
2003
In mature cortex, activation of the cholinergic system induces oscillatory network activity and facilitates synaptic plasticity. We used an in vitro preparation of the intact cerebral cortex and cortical slices of the neonatal rat to study carbachol (CCh, >or=30 micro M)-induced network oscillations during the early postnatal period. Multi-site extracellular recordings revealed CCh-induced transient beta oscillations with an average duration of 4.6 +/- 0.2 s, amplitude of 123 +/- 7.4 microV and frequency of 17.7 +/- 0.5 Hz. These oscillations propagated uniformly at 0.5-1.5 mm/s over the cortex and were reversibly blocked by tetrodotoxin (TTX) and atropine, indicating that they depended on …
Control of cortical neuronal migration by glutamate and GABA
2015
Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist …
Activation of metabotropic glutamate receptors induces propagating network oscillations in the intact cerebral cortex of the newborn mouse.
2006
Activation of metabotropic glutamate receptors (mGluRs) with (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) elicited in the frontal or occipital pole of the intact cerebral cortex preparation of the newborn mouse (P0-P3) a transient oscillatory field potential activity in the frequency range of 11-14Hz. These oscillations propagated over the whole cortical hemisphere and were blocked by tetrodotoxin, indicating that action potentials are required for the generation of this activity. Blockade of GABA-A receptors with gabazine did not influence the ACPD-induced network activity, but the glycine antagonist strychnine caused a significant decrease in the frequency, amplitude and durat…
Mild systemic inflammation and moderate hypoxia transiently alter neuronal excitability in mouse somatosensory cortex
2016
During the perinatal period, the brain is highly vulnerable to hypoxia and inflammation, which often cause white matter injury and long-term neuronal dysfunction such as motor and cognitive deficits or epileptic seizures. We studied the effects of moderate hypoxia (HYPO), mild systemic inflammation (INFL), or the combination of both (HYPO + INFL) in mouse somatosensory cortex induced during the first postnatal week on network activity and compared it to activity in SHAM control animals. By performing in vitro electrophysiological recordings with multi-electrode arrays from slices prepared directly after injury (P8–10), one week after injury (P13–16), or in young adults (P28–30), we investig…
Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands
2016
The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs - but not the antidepressant citalopram - countered PCP-evoked fall of LFO in the medial prefron…
Connexin-30 mRNA Is Up-Regulated in Astrocytes and Expressed in Apoptotic Neuronal Cells of Rat Brain Following Kainate-Induced Seizures
2002
Glial connexins (Cxs) make an extensively interconnected functional syncytium created by a network of gap junctions between astrocytes and oligodendrocytes. Among Cxs expressed in the brain, Cx30 is expressed in grey matter astrocytes, as shown at the protein level by immunoistochemistry. In the present study we aimed to perform a detailed study of the regional distribution of Cx30 mRNA in the adult and postnatal developing rat brain, analyzing its expression by in situ hybridization, and determining its cell type localization by double labeling. Recently, it has been suggested that neuronal activity may control the level of intercellular communication between astrocytes through gap junctio…