Changes In Glutamate Receptors Research Articles

Developmental changes in glutamate receptor stimulated inositol phospholipid metabolism and 45Ca 2+-accumulation in posthatch chicken forebrain

In chicken forebrain the two phases of synapse development, formation and maturation, are temporally well separated. We have used this model system to determine the developmental profile of glutaminergic activation of phosphoinositidase C. Stimulation of [ 3H]inositol-loaded forebrain prisms by quisqualic acid (QA; 30 μM), or the metabotropic agonist 1-aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD; 30 μM), significantly increased [ 3H]inositol phosphate production. This response progressively decreased with developmental age, with the largest (approximately 3-fold) decrease occurring between 21 days and adult (>10 weeks). In contrast, QA (30 μM) stimulated a quite distinct developmental profile for 45Ca 2+ accumulation, with the response being maximal between 7 and 14 days before declining sharply to adult levels by 21–25 days. These results demonstrate that there is a major decrease in metabotropic glutamate receptor activation of phosphoinositidase C during the maturation phase of synapse development.

Changes in glutamate receptor and proenkephalin gene expression after kindled seizures

Changes in gene expression after kindled seizures were examined using microdissection of discrete brain areas and Northern and slot blot analyses. Experimental animals were kindled with either of two protocols: (1) a paradigm in which 50 Hz/10 s stimulus trains were delivered every 30 min through hippocampal electrodes (12 stimulations every other day for 4 days) and (2) a traditional approach in which 50 Hz/10 s stimulus trains were given to the hippocampus three times daily for 16 days. Rats were sacrificed 24 h or 30 days after the last kindled seizure. We first examined the possibility that kindling may affect transcription of mRNA for neurotransmitter receptors. We found significant decreases (22–58%) in AMPA/kainate activated glutamate receptor mRNAs (GluR1, -2, -3 mRNAs) in hippocampus, amygdala/entorhinal cortex and in frontoparietal cortex 24 h but not 30 days after rapidly kindled seizures. However, changes in GABA receptor α 1, α 2, α 4 or β 1 mRNAs were not observed in any brain region 30 days after traditional kindling or 24 h after rapidly kindled seizures. In addition, we tested whether changes in the expression of proenkephalin could be detected after kindling. We found significant increases (1.7–10 fold) in proenkephalin mRNA in the frontoparietal cortex, hippocampus and in the amygdala/entorhinal cortex 24 h but not 30 days after rapidly kindled seizures. Our findings suggest that changes in glutamate receptor and proenkephalin gene expression are robust, acute sequelae to kindled seizures and may be involved in kindling.

P-121 - Changes of glutamate receptors and c-fos expression in the brain of phenobarbital-dependent and withdrawn rats.

P-121 - Changes of glutamate receptors and c-fos expression in the brain of phenobarbital-dependent and withdrawn rats.

Postischemic functional changes of glutamate receptors in field CA1 of the gerbil hippocampus

Postischemic functional changes of glutamate receptors in field CA1 of the gerbil hippocampus

Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus

The NMDA and AMPA receptors have been shown to play critical roles in various forms of synaptic plasticity (learning and memory, long-term potentiation). The present study investigated the involvement of these two receptors in a well-characterized classical conditioning paradigm. Following classical conditioning of the rabbit nictitating membrane the binding properties of these two subclasses of excitatory amino acid transmitter receptors were analyzed in dorsal hippocampi by quantitative autoradiography. [ 3H]TCP and [ 3H]AMPA were used to identify the NMDA and AMPA receptors, respectively. The binding of [ 3H]TCP to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of the conditioned and unconditioned stimuli resulted in increased [ 3H]AMPA binding to the AMPA receptor in several subfields of the hippocampus, while unpaired presentations had no significant effects. The increase in binding was due to an increased affinity of the low-affinity component of the AMPA receptor. The results support the hypothesis that changes in glutamate receptors participate in the synaptic plasticity involved in certain forms of learning.

Glutamate receptor changes in brain synaptic membranes from human alcoholics

Brains from human alcoholics and non-alcoholics were obtained shortly after death. The hippocampus was dissected, homogenized, and processed for the isolation of a synaptic membrane-enriched fraction and the study of L-[3H]glutamic acid and 3-((+-)-2-carboxypiperazin-4-yl)-[1,2(3H)propyl-1-phosphonic acid ([3H]CPP) binding sites. The pharmacological characteristics of L-[3H]glutamic acid binding to synaptic membranes isolated from hippocampus corresponded to the labeling of a mixture of N-methyl-D-aspartate (NMDA), kainate and quisqualic acid receptor sites. Synaptic membranes prepared from the hippocampus of individuals classified as alcoholics had significantly higher density of glutamate binding sites than identically prepared membranes from non-alcoholic individuals. In addition, there was a clear definition of a population of L-glutamate binding sites (approx. 10% of total) in the membranes from alcoholics that had a higher affinity for the ligand than the major set of sites labeled in membranes from both alcoholics and non-alcoholics. Neither the age of the individuals at the time of death nor the time that elapsed between death and processing of brain tissue were significant factors in determining either recovery of purified synaptic membranes from brain homogenates or L-[3H]glutamate binding to synaptic membranes. In order to determine whether some of the changes in L-[3H]glutamic acid binding were due to alterations in binding at the NMDA receptor subtype, we also measured binding of [3H]CPP to extensively washed crude synaptosomal membranes. Membranes from brains of alcoholics had higher affinity (3-fold) for [3H]CPP but lower binding capacity (3-fold) when compared with those of non-alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

L-Leucine prevents ammonia-induced changes in glutamate receptors in the brain and in visual evoked potentials in the rabbit.

The effect of L-leucine on glutamate receptors in the brain and on visual evoked potentials was studied in hyperammonemic rabbits. Hyperammonemia was induced by the iv infusion of 2.1 mmol NH4Cl/h over 3 hr. Hyperammonemia was followed by a 116% increase in the specific binding of 3H-glutamate to synaptic membranes prepared from the hippocampus. This increase was due to both an increase in the affinity and in the density of the glutamate receptor. The simultaneous infusion of L-leucine (6.7 mmol/hr) completely prevented the ammonia-induced increase in the specific glutamate binding, whereas L-valine and D-leucine had no effect. Hyperammonemia was also associated with typical, reproducible, and reversible changes in visual evoked potentials. The amplitudes of the first negative and the second positive peak decreased, whereas the latencies of these peaks remained unchanged. The simultaneous infusion of L-leucine completely prevented these changes. These findings indicate (1) that L-leucine prevents ammonia-induced changes in the glutamatergic excitatory neurotransmitter system and (2) that pharmacologic doses of L-leucine modulate the effects of hyperammonemia on central neurotransmission as assessed by visual evoked potentials. A causal relationship between the effects of L-leucine on ammonia-induced changes in glutamate receptors and in visual evoked potentials cannot be inferred with confidence. These findings provide a potential alternative explanation for the apparent beneficial effects of infusions of branched-chain amino acids on hepatic encephalography in patients with chronic liver disease.

Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit.

The status of the excitatory glutamatergic neurotransmitter system in hepatic encephalopathy has been studied. Synaptic membranes (SM) were prepared from the brains of normal rabbits, hyperammonemic normal rabbits, and rabbits with fulminant hepatic failure. Data on the specific binding of glutamate to SM indicated that fulminant hepatic failure was associated with a decrease in the number of glutamate receptors on SM from cerebral cortex, cerebellum, and particularly the hippocampus, without any associated change in the affinity of these receptors. In contrast, hyperammonemia was associated with an increase in the affinity and no decrease in the number of glutamate receptors on SM from the hippocampus. These findings indicate that the effects of hyperammonemia and fulminant hepatic failure on cerebral glutamate receptors are fundamentally different. The decreased number of glutamate receptors in hepatic encephalopathy might reflect a decreased sensitivity of glutamatergic neurons to glutamate-mediated neural excitation, a phenomenon that could contribute to the neural inhibition of hepatic encephalopathy.