Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that suppression of inward calcium current in presynaptic terminals is the cause of failure of synaptic transmission early during cerebral hypoxia. Postsynaptic responses in CA1 zone of hippocampal tissue slices were blocked either by the combined administration of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 3-((+-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP) or by lowering extracellular calcium concentration ([Ca2+]o). Repetitive orthodromic activation of central neurons caused transient decrease of [Ca2+]o (measured by ion selective microelectrodes) in neuropil, attributable to influx of Ca2+ in presynaptic terminals. Presynaptic [Ca2+]o responses were rapidly and reversibly suppressed when oxygen was withdrawn from hippocampal tissue slices. The 'resting' baseline level of [Ca2+]o declined at first gradually, then precipitously as in spreading depression (SD). Presynaptic volleys during high frequency train stimulation were also depressed somewhat before SD began. We conclude that (1) presynaptic Ca2+ currents fail during hypoxia, perhaps because 'resting' intracellular free Ca2+ activity is increased and, in part, also because of partial failure of presynaptic impulse conduction; (2) the influx of Ca2+ into brain cells in hypoxic spreading depression is not mediated by glutamate/aspartate dependent channels.
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PMID:Suppression of presynaptic calcium currents by hypoxia in hippocampal tissue slices. 131 7

Spontaneous episodes of spreading depression (SD) were observed in the CA3 subfield of immature or young (2-30 days postnatally) hippocampal slices perfused with medium containing 4-aminopyridine (4-AP, 50 microM). SD appeared in 34% of the hippocampal slices examined and was more frequently observed in slices obtained from 11 to 20-day-old animals. SD studied with extracellular field potential recordings consisted of large amplitude (18.7 +/- 1.1 mV, mean +/- S.E.M.) negative DC shifts that lasted 30-250 s. Unlike the epileptiform activity that was concomitantly seen during 4-AP application, SD was blocked by the NMDA receptor antagonist 3-((RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP, 2-10 microM). In contrast, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 5 microM), a non-NMDA-type receptor antagonist, blocked the epileptiform activity but only increased the interval between SD episodes. These results demonstrate that immature hippocampal tissue is susceptible to SD episodes, when perfused with 4-AP-containing medium, and that the occurrence of these episodes presumably depends on the activation of the NMDA receptor. In addition these findings indicate that SD shows a sensitivity to excitatory amino acid receptor antagonists that differs from that of the epileptiform activity recorded simultaneously.
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PMID:CPP, an NMDA-receptor antagonist, blocks 4-aminopyridine-induced spreading depression episodes but not epileptiform activity in immature rat hippocampal slices. 134 14

In vivo voltammetry at electrochemically pretreated carbon fibre electrodes was used to investigate the effect of intracerebroventricular (i.c.v.) administration of N-methyl-D-aspartic acid (NMDA) on neuronal activity in rat nucleus accumbens. Infusion of a low dose of NMDA (1 nmol) was followed a few minutes later by rapid changes in both Peak 1 and Peak 2 heights indicating large but short-lived increases in the extracellular concentrations of ascorbate and catecholamines, respectively. These responses did not seem to be dependent on the dose infused since infusion of NMDA for a longer time period neither changed the amplitude nor the time-course of these effects. The increase in Peak 2 height was resistant to pargyline pretreatment indicating that this response mainly reflected the release of dopamine. The administration of NMDA was followed by behavioural activation in the animals but not convulsions. Co-administration of the competitive NMDA receptor antagonist, CPP (1 nmol), completely blocked these effects while the acetylcholine receptor antagonist, atropine (1.5 nmol), and the GABA receptor antagonist, picrotoxin (1 nmol), failed in this respect. The phenomenon spreading depression is discussed as a possible explanation of these results.
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PMID:Rapid changes in ascorbate and dopamine release in rat nucleus accumbens after intracerebroventricular administration of NMDA. 152 Nov 53

Spreading depression-like neuron depolarization was induced in CA1 of hippocampal tissue slices by irrigation with artificial cerebrospinal fluid containing 133.5 mM K+ for 8-40 min. Evoked responses disappeared during irrigation with high-K+ solution. Following 8-20 min irrigation orthodromic responses showed a triphasic recovery cycle: early partial return with evidence of neuron hyperexcitability, then secondary depression and finally slow partial recovery. After 30 min or more of high-K+ exposure, ortho- and antidromic responses remained severely depressed for at least 5.5 to 6.5 h. When, however, the tissue was deprived of calcium, or N-methyl-D-aspartate (NMDA) receptors were blocked by 10 microM 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), then evoked responses recovered partially after a 30- or 40-min high-K+ exposure. Post-exposure hyperexcitability was not prevented by CPP. We conclude that prolonged depolarization by elevated K+ causes irreversible neuron damage, which is triggered or accelerated by influx of calcium ions into neurons, mediated in part by NMDA receptor activation.
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PMID:Lasting neuron depression induced by high potassium and its prevention by low calcium and NMDA receptor blockade. 166 Jul 51

Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.
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PMID:The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury. 169 51

Brief (5 min) bilateral carotid occlusion in the gerbil produces forebrain ischemia resulting, as previously reported, in almost complete neuronal loss in the CA1 region of the hippocampus; this neuronal destruction occurs between the 4th and 7th day post-ischemia. Various hippocampal biochemical indices were measured from just after such ischemia to 21 days of recirculation, and the temporal pattern of changes compared with that of cell loss. The level of thiobarbiturate reacting substances (TBARS), a measure of lipid peroxidation, was greatly elevated at 30 min after ischemia, rapidly returned to normal levels (by 60 min), but was again elevated on days 4-14. The beginning of this second period of elevation correlated closely with the onset of neuronal loss and the very abrupt and large (to about 32%) decrease in specific N-methyl-D-aspartate (NMDA) binding sites, measured with radioactive CPP. The number of muscarinic binding sites, measured with radioactive quinuclidinyl benzilate, showed an even greater decrease (to 13%) at 21 days post-ischemia, but the decrease was delayed (starting at day 7) and much more gradual than the loss in NMDA binding. In neither case was there any change in binding affinity at any time studied. Acetylcholine (ACh) concentrations were initially greatly decreased (to about 15% at 5 min), transiently increased (to about 130% at 30 min), and then decreased again (to about 15% at 60 min), after which gradual recovery occurred and was completed by day 14. Since no inhibition of choline acetyltransferase activity was observed at any time, the reversible depression in ACh must depend upon some factor other than loss of this key synthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time course of changes in lipid peroxidation, pre- and postsynaptic cholinergic indices, NMDA receptor binding and neuronal death in the gerbil hippocampus following transient ischemia. 182 14

A 10-min bilateral carotid occlusion (BCO) in Mongolian gerbils induces transient generalized epileptic discharges in the hippocampal and cortical regions, which are followed by long lasting interictal spiking activity. An initial peak of this activity occurs within 18-36 h after BCO, then it decreases slowly and completely disappears by the 6th-7th day. On the 7th day, morphological evidence shows a selective loss of CA1 hippocampal neurons. 4-(3-Phosphonopropyl)-2-piperazine-carboxylic acid (CPP), a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor was administered (7 or 15 mg/kg i.p.) immediately after clamping, and again every 12 h for 3 consecutive days. It induced a dose-related depression of epileptic activity, while, on the other hand, at both dosages, it always prevented the loss of CA1 neurons. The results are discussed in view of the different mechanisms mediating cell damage and epileptic activity.
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PMID:Epileptic activity following cerebral ischemia in Mongolian gerbils is depressed by CPP, a competitive antagonist of the N-methyl-D-aspartate receptor. 183 55

Meta-Chlorophenylpiperazine (m-CPP), a serotonin agonist and metabolite of the anti-depressant trazodone, was administered chronically to eight moderate to severely affected Alzheimer patients to determine whether it would produce improvement in behavioral symptoms complicating this illness. In doses up to 80 mg/day for 16 days, m-CPP was well tolerated and resulted in small but significant increases in anergy and depression-related symptoms compared with placebo. The effects of chronic m-CPP in this study contrast with the reported beneficial effects of the parent compound trazodone and selective 5-HT reuptake inhibitors in treating behavioral symptoms in Alzheimer patients.
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PMID:A pilot placebo-controlled study of chronic m-CPP administration in Alzheimer's disease. 191 5

Systemic administration of selective NMDA antagonists, such as CPP, APH, ketamine and MK-801, increased spontaneous gastric motility of the rat in a dose-dependent manner, and they prevented the NMDA-evoked depression of gastric motility. On the other hand, a broad spectrum excitatory amino acid antagonist, kynurenate, DNQX and CNQX decreased spontaneous gastric motility. Under the action of hexamethonium or chlorisondamine, CPP and MK-801 had little effect upon gastric motility. After the treatment with atropine, the motor responses to NMDA, CPP and MK-801 were hardly observed. Similar results were obtained after vagotomy.
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PMID:Selective N-methyl-D-aspartate (NMDA) antagonists increase gastric motility in the rat. 197 72

Excitatory synaptic field potentials, induced by stimulating optic nerve fibers, were recorded from in vitro preparations of the optic tectum of the frog. Bath-applied N-methyl-D-aspartate (NMDA), glutamate or quisqualate elicited transient enhancement in these field potentials, followed by a sustained depression reversible on washout. Responses to glutamate or quisqualate and the amplitude of control synaptic potentials, were not affected by the NMDA receptor antagonists aminophosphonovalerate (APV), 3(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), ketamine, magnesium ions or dizocipiline (MK 801) which, on the other hand, blocked the effects of NMDA. The antagonist dinitroquinoxaline-2,3-dione (DNQX), which is preferential for non-NMDA receptors, blocked the action of glutamate and synaptic transmission. In the presence of strychnine, glycine reversed the block of NMDA-mediated responses caused by magnesium. It is suggested that in the optic tectum of the frog, glutamate is the excitatory transmitter of at least one class of optic nerve fibers and that it acts through non-NMDA receptors. Although this area of the brain contains a well-developed NMDA receptor system, its function in physiological synaptic transmission remains to be elucidated.
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PMID:An electrophysiological study of the action of N-methyl-D-aspartate on excitatory synaptic transmission in the optic tectum of the frog in vitro. 197 14


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