Development of cytotoxic cerebral edema in rats following intracaudatum injection of tACPD, an agonist of metabotropic glutamate receptors.
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OBJECTIVE: To explore the involvement of metabotropic glutamate receptors (mGluRs) in the formation of cerebral edema. METHODS: Male Wistar rats weighing from 250 g to 300 g were used. Trans-1-aminocyclopentane-1, 3-diacarboxylic acid (tACPD), an agonist of mGluRs, was microinjected into the right caudatum. Brain water content was determined by a wet weight/dry weight technique and Na+, K+ and Ca2+ contents were measured by inductive Couple Plasma-9000 at 6 h, 24 h and 48 h post-injection. Extravasation of Evan's blue (EB) into the brain was determined as an indicator of disturbance in the blood-brain barrier (BBB) and endothelial cells. Histologic studies were performed under a Leitz microscope and a Philips EM208s electron microscope. RESULTS: Dose-dependent and time-related increase of brain water was induced after tACPD (10, 50, 500 and 1000 nmol) injection. A significant increase in Na+ and K+ content but not in Ca2+ content was observed. EB extravasation showed no blue stain, indicating no increase in BBB permeability induced by tACPD-injection. Electron microscope study confirmed this finding and revealed remarkable swelling of astrocytes especially endfoot processes of astrocytes around capillaries at 6 h after tACPD-injection. In addition, all changes mentioned above occurred in both caudatum. CONCLUSION: These results indicate that activation of mGluRs by tACPD injected into the caudatum induced cytotoxic brain edema and interfered with astrocyte K+ buffering. This may provide new clues for therapeutic intervention. (+info)
Cellular mechanisms of the slow (<1 Hz) oscillation in thalamocortical neurons in vitro.
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The slow (<1 Hz) rhythm is a defining feature of the electroencephalogram during sleep. Since cortical circuits can generate this rhythm in isolation, it is assumed that the accompanying slow oscillation in thalamocortical (TC) neurons is largely a passive reflection of neocortical activity. Here we show, however, that by activating the metabotropic glutamate receptor (mGluR), mGluR1a, cortical inputs can recruit intricate cellular mechanisms that enable the generation of an intrinsic slow oscillation in TC neurons in vitro with identical properties to those observed in vivo. These mechanisms rely on the "window" component of the T-type Ca(2+) current and a Ca(2+)-activated, nonselective cation current. These results suggest an active role for the thalamus in shaping the slow (<1 Hz) sleep rhythm. (+info)
Developmental changes in the modulation of cyclic amp accumulation by activation of metabotropic glutamate receptors.
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Physiological functions of glutamic acid, the major neurotransmitter in the central nervous system, are mediated by the two receptor families: ionotropic glutamate receptors (iGluRs), and metabotropic glutamate receptors (mGluRs). Eight mGluR subtypes (mGluR1-mGluR8), together with splice variants, have been identified and classified into three groups. One of the features of mGluRs is their profile of functional expression throughout postnatal development. Several lines of evidence suggest age-dependent differences in the pattern or amount of mGluR-mediated phosphatidylinositol (P1) turnover as well as in the expression of mGluRs. The aim of the present study was to investigate how the different effects of mGluR agonists on cAMP accumulation change during rat postnatal life. We have found that the stimulatory effect of glutamate and/or 1S,3R-ACPD on cAMP accumulation predominates in young animals and decreases in the adults. We have also shown that the enhancement of the effect of noradrenaline on cAMP accumulation by 1S,3R-ACPD in rats is an age-dependent phenomenon which reaches its maximum in 14-30-day-old rats and gradually decreases during their maturation. On the basis of our studies, we conclude that the activation of mGluRs resulting in cAMP accumulation depends on the age of an animal. (+info)
Stereoselective synthesis of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid via C-H insertion of alkylidenecarbene.
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(1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD), a potent agonist of metabotropic glutamate receptors, was synthesized from L-serine. The chiral quaternary center was constructed by C-H insertion of the alkylidenecarbene, this being generated by the reaction between lithiotrimethylsilyldiazomethane and the corresponding ketone. (+info)
Transport of amino acids by isolated gills of the mussel Mytilus californianus Conrad.
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The unidirectional influx of cycloleucine into in vitro preparations of gill tissue of the mussel, Mytilus californianus, was determined. Influx was found to be linear for at least an hour, and the kinetics of cycloleucine influx conformed to Michaelis-Menten type kinetics. The transport mechanism(s) for cycloleucine is relatively specific for the L-enantiomorph of neutral amino acids, and is capable of accumulating cycloleucine to intracellular concentrations much higher than those of the surrounding medium. Evedence is presented that the transport of amino acids by gill tissue plays a significant role in whole animal nutrition. (+info)
Effects of excitatory modulation on intrinsic properties of turtle motoneurons.
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The purpose of this study was to quantify the effects of excitatory modulation on the intrinsic properties of motoneurons (MNs) in slices of spinal cord taken from the adult turtle. Responses were noted following application of an excitatory modulator: serotonin (5-HT), muscarine, trans-1-amino-1,3-cyclopentane dicarboxylic acid (tACPD), or all three combined. A sample of 44 MNs was divided into 2 groups, on the basis of whether MNs did (28/44) or did not (16/44) demonstrate a nifedipine-sensitive acceleration of discharge during a 2-s, intracellularly injected stimulus pulse. Such acceleration indicates the development of a plateau potential (PP). Excitatory modulation lowered the MNs' resting potential, increased input resistance, decreased rheobase, reduced several afterhyperpolarization values, and shifted the conventional, one-phase stimulus current-spike frequency (I-f) relation to the left. For both MN groups, the relative efficacy of excitatory modulation on both non-PP and PP MNs was generally in the following order: combined application > 5-HT approximately muscarine > tACPD. In many instances, the effects of modulation differed significantly for non-PP versus PP MNs, the most pronounced being in their I-f relation. To describe this difference, it was necessary to measure a two-phase relation. In PP MNs, excitatory modulation considerably increased the slope of the first (initial) phase and flattened the second (later) phase of this relation. The latter result bore similarities to that obtained in a previous study, which addressed MN firing behavior during fictive locomotion of the high-decerebrate cat. (+info)
Spatial segregation and interaction of calcium signalling mechanisms in rat hippocampal CA1 pyramidal neurons.
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Postsynaptic [Ca2+]i increases result from Ca2+ entry through ligand-gated channels, entry through voltage-gated channels, or release from intracellular stores. We found that these sources have distinct spatial distributions in hippocampal CA1 pyramidal neurons. Large amplitude regenerative release of Ca2+ from IP3-sensitive stores in the form of Ca2+ waves were found almost exclusively on the thick apical shaft. Smaller release events did not extend more than 15 microm into the oblique dendrites. These synaptically activated regenerative waves initiated at points where the stimulated oblique dendrites branch from the apical shaft. In contrast, NMDA receptor-mediated increases were observed predominantly in oblique dendrites where spines are found at high density. These [Ca2+]i increases were typically more than eight times larger than [Ca2+]i from this source on the main aspiny apical shaft. Ca2+ entry through voltage-gated channels, activated by backpropagating action potentials, was detected at all dendritic locations. These mechanisms were not independent. Ca2+ entry through NMDA receptor channels or voltage-gated channels (as previously demonstrated) synergistically enhanced Ca2+ release generated by mGluR mobilization of IP3. (+info)
Glutamate induces different neuronal conditioned responses than ACPD when used as a locally ionophoresed unconditioned stimulus in the cat motor cortex.
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Single unit recordings were made from the motor cortex of conscious cats with glass micropipettes that allowed ionophoretic application of 0.5 M glutamate in 2 M NaCl or 0.5 M ACPD (1S,3R-1-amino-cyclopentane-1,3-dicarboxylic acid, a mGluR agonist) in 2 M NaCl. Activity in response to a 70 dB click (1 ms rectangular pulse to loudspeaker) was studied before, during, and immediately after applying each agent locally as a paired US (90 nA current 570 ms after click for 300 ms in combination with glabella tap). A 70 dB hiss sound was presented 4.4 sec after the click as a discriminative stimulus (DS). CS and DS were presented 10 times initially (adaptation); then CS, US plus tap, and DS (approximately 10 times as conditioning); and then CS and DS (2-10 times to test post-conditioning). Glutamate potentiated the mean, early, 8-16 ms response to the click after conditioning (t=18.2, p<0.0001), but not the baseline activity which decreased from a mean of 17 spk/sec to 7 spk/sec (t=3.71, p<0.001). Baseline activity increased to 31 spk/sec when glutamate was applied during conditioning (t=3.30, p<0.005). ACPD reduced the intermediate, 64-72 ms response to the click after conditioning (t=8.18, p<0.0001), and potentiated the late 104-112 ms response (t=15.4, p<0.0001). Baseline activity was slightly increased after conditioning with ACPD. Saline did not potentiate the response to click. The results indicate that glutamate agonists that differ in their receptor affinities can induce different CRs when used as locally applied USs to condition neuronal responses to a click CS in the motor cortex of cats. (+info)