Search results for " AMPA"
showing 10 items of 41 documents
Effects of CNQX and MPEP on sensitization to the rewarding effects of morphine
2011
The present study was conducted to evaluate the influence of the glutamatergic receptors α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic glutamate 5 (mGlu5) receptors on sensitization to the rewarding effects of morphine. The effects of pre-treatment with saline or 20 mg/kg morphine plus the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (5 or 10 mg/kg) or the metabotropic Glu5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) (5 or 10 mg/kg) on the place conditioning induced by a low dose of morphine (2 mg/kg) were assessed. The 2 mg/kg dose of morphine was ineffective in animals pre-treated with saline but induced a clear con…
Novel Potent Anticonvulsant Agent Containing a Tetrahydroisoquinoline Skeleton
2006
In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure-activity relationships. All derivatives were evaluated against audiogenic seizures in DBA/2 mice, and the 1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl) derivative (26) showed the highest activity with a potency comparable to that of talampanel, the only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.
2019
AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a dec…
Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on the rewarding properties of MDMA in mice
2019
Exposure to social stress alters the response to drugs of abuse of experimental animals. Changes in the glutamatergic system seem to play a role in the effects of social defeat stress on the rewarding properties of cocaine and amphetamine. The aim of the present study was to evaluate the involvement of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the effects of social defeat on the conditioned place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our hypothesis was that changes in these receptors could mediate the effects of social defeat on MDMA reward. Young adult male mice were exposed to an episode…
Activation of a ΔFOSB dependent gene expression pattern in the dorsolateral prefrontal cortex of patients with major depressive disorder
2010
Abstract Background A ΔFOSB mediated transcriptional response in the nucleus accumbens (NAc) is induced by chronic social stress in rodent and a 50% down-regulation of ΔFOSB has been also reported in the NAc of eight depressed subjects. To evaluate the role of ΔFOSB in the prefrontal cortex which is critically involved in negative cognitive bias associated with major depressive disorder (MDD) we have quantified the mRNA levels of ΔFOSB and of five of its major target genes in the Brodmann area 46 from 24 patients with MDD (11 with psychotic symptoms) and 12 controls. Method Expression of the six genes has been quantified by a real-time quantitative PCR method: ΔFOSB , GRIA2 (encoding the Gl…
Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implicatio…
2009
Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subuni…
Transient oligemia is associated with long-term changes in binding densities of cortical inhibitory GABAA receptors in the rat brain
2009
Recently, we could demonstrate in rats that a short transient oligemic period of only 20-minute duration, induced by systemic hypotension, resulted in a transient decline of spatial memory capacities without any histological damage over a subsequent period of 6 months. In our present study, we checked for more subtle alterations within the highly vulnerable hippocampal CA1 subfield using quantification of neuronal cell density and semi-quantitative analysis of the ischemia-sensitive protein MAP2. Since hippocampal excitatory and inhibitory neurotransmitter receptors are crucially involved in spatial memory processes, quantitative in vitro receptor autoradiography was performed using [(3)H]M…
Pravastatin treatment causes a shift in the balance of hippocampal neurotransmitter binding densities towards inhibition
2009
Since pravastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce infarct volumes and glutamate release in a rat model of ischemic stroke, the aim of the present study was to investigate whether this neuroprotective effect may be due to a modulation of excitatory and inhibitory neurotransmitter receptors. Therefore, Wistar rats were treated six times in 4 days with pravastatin or saline and allowed to survive for 6 hours or 5 days (n=10 per time point and group), respectively. Using quantitative receptor autoradiography, ligand binding densities of [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors were analyzed in sensorimotor c…
Frequency constrained optimal Power Flow based on Glow-worm Swarm Optimization in Islanded Microgrids
2015
This work presents an application of a swarm optimization method to solve the optimal power flow problem taking into account the constraints of frequency and line ampacity in three-phase islanded Microgrids. Each generation unit is equipped with a Power Electronics Interface. In the considered formulation, the droop control parameters are considered as variables to be adjusted by a higher control level, while the frequency is kept in rated bounds. Another typical constraint for OPF formulation, the max ampacity of each line, is also considered. Two case studies with different dimensions and electrical features have been considered and the obtained results show the efficiency of the proposed…
Ligand-binding domain determines endoplasmic reticulum exit of AMPA receptors.
2010
AMPA receptors (AMPARs) are tetrameric ion channels that mediate rapid glutamate signaling in neurons and many non-neuronal cell types. Endoplasmic reticulum (ER) quality control mechanisms permit only correctly folded functional receptors to be delivered to the cell surface. We analyzed the biosynthetic maturation and transport of all 12 GluA1–4 subunit splice variants as homomeric receptors and observed robust isoform-dependent differences in ER exit competence and surface expression. In contrast to inefficient ER exit of both GluA3 splice forms and the flop variants of GluA1 and GluA4, prominent plasma membrane expression was observed for the other AMPAR isoforms. Surprisingly, deletion …