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)

Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.
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PMID:Psychotherapeutic benefits of opioid agonist therapy. 1895 29

Activation of N-methyl-d-aspartic acid (NMDA) glutamate receptors (NMDARs) is required for long-term potentiation (LTP) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular mechanisms of learning and memory. We demonstrate here that a brief bath co-application of a low concentration of NMDA, an agonist of NMDARs, and the selective antagonist of NR2B-containing NMDARs, (alpha R, beta S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol (Ro25-6981), to hippocampal slices from young adult rats produced a slowly developing LTP persisting at least for 6 h following a transient depression of synaptic transmission in CA1 synapses. The LTP was likely to occur at postsynaptic site and was initiated by activation of NMDARs, and its development was mediated by cAMP-dependent protein kinase (PKA) activation and protein synthesis. This chemically induced LTP and the tetanus-induced late phase of LTP (L-LTP) were mutually occluding, suggesting a common expression mechanism. Thus, we have demonstrated that a brief bath co-application of NMDA with Ro25-6981 to a slice offers an alternative to electrical stimulation as a stimulation method to induce L-LTP. The chemically induced LTP did not require the low-frequency test stimulation typically used to monitor the strength of synapses during and after drug application. Thus, the LTP may occur at a large fraction of synapses in the slice and not to be confined to a small fraction of the synapses where electrical stimulation can reach and induce LTP. Therefore, this chemically induced LTP may be useful for assessing the biochemical and morphological correlates and the molecular aspects of the expression mechanism for L-LTP that has been proven to correlate to hippocampal long-term memory.
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PMID:Late phase of long-term potentiation induced by co-application of N-methyl-d-aspartic acid and the antagonist of NR2B-containing N-methyl-d-aspartic acid receptors in rat hippocampus. 1901 Mar 96

In mice lacking the blood coagulation regulator thrombomodulin, fibrinolytic degradation products (FDP) of fibrin induce apoptotic cell death of a specialized cell type in the placenta, polyploid trophoblast giant cells. Here, we document that this bioactivity of FDP is conserved in human FDP, is not limited to trophoblast cells, and is associated with an Aalpha-chain segment of fibrin fragment E (FnE). The majority of proapoptotic activity is arginine-glycine-aspartic acid (RGD)-independent and requires caveolin-1-dependent cellular internalization of FnE. Internalization through caveoli is mediated by an epitope contained within Aalpha52-81 that is necessary and sufficient for cellular uptake of FnE. Aalpha52-81 does not cause apoptosis itself, and competitively inhibits FnE internalization and apoptosis induction. Apoptotic activity per se resides within Aalpha17-37 and requires the N-terminal neoepitope generated by release of fibrinopeptide A. Cellular internalization of FnE elicits depression of mitochondrial function and consequent apoptosis that is strictly dependent on the activity of caspases 9 and 3. These findings describe the molecular details of a novel mechanism linking fibrin degradation to cell death in the placenta, which may also contribute to pathologic alterations in nonplacental vascular beds that are associated with fibrinolysis.
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PMID:Caveolin-1-dependent apoptosis induced by fibrin degradation products. 1940 99

Previous studies in children with diabetes found that hyperglycemia induces memory dysfunction. In this study, we investigated memory and synaptic plasticity in streptozotocine (STZ)-induced diabetic rats during the juvenile period. We further investigated the effects of glucagon-like peptide-1 (GLP-1) on the diabetes-induced profiles. STZ (85 mg/kg, i.p.) was administered to 17-day-old Wistar rats to induce type-1 juvenile diabetes mellitus (JDM). In the Y-maze test, JDM rats showed significant impairment of learning and memory, which were improved by GLP-1 (7-36) amide (1 microg/5 microl/rat, i.c.v.). Extracellular recording at Schaffer collateral synapses in the CA1 region of hippocampal slices showed that long-term potentiation and paired-pulse facilitation in JDM rats were similar to age-matched control rats. However, the input-output relation was strengthened, and long-term depression (LTD) and responses of N-methyl d-aspartic acid through NR2B subunits were weakened in the JDM rats. GLP-1 (7-36) amide (100 nM) increased the magnitude of LTD and the responses through NR2B in the JDM rats. These results indicate that the lack of LTD and NR2B responses may contribute to impairment of memory associated with JDM, suggesting the potential usefulness of GLP-1 in the treatment of memory dysfunction in JDM.
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PMID:The influences of juvenile diabetes on memory and hippocampal plasticity in rats: improving effects of glucagon-like peptide-1. 1932 Nov 33

Oxygen and glucose deprivation (OGD) induces delayed cell death in hippocampal CA1 neurons via Ca(2+)/Zn(2+)-permeable, GluR2-lacking AMPA receptors (AMPARs). Following OGD, synaptic AMPAR currents in hippocampal neurons show marked inward rectification and increased sensitivity to channel blockers selective for GluR2-lacking AMPARs. This occurs via two mechanisms: a delayed down-regulation of GluR2 mRNA expression and a rapid internalization of GluR2-containing AMPARs during the OGD insult, which are replaced by GluR2-lacking receptors. The mechanisms that underlie this rapid change in subunit composition are unknown. Here, we demonstrate that this trafficking event shares features in common with events that mediate long term depression and long term potentiation and is initiated by the activation of N-methyl-d-aspartic acid receptors. Using biochemical and electrophysiological approaches, we show that peptides that interfere with PICK1 PDZ domain interactions block the OGD-induced switch in subunit composition, implicating PICK1 in restricting GluR2 from synapses during OGD. Furthermore, we show that GluR2-lacking AMPARs that arise at synapses during OGD as a result of PICK1 PDZ interactions are involved in OGD-induced delayed cell death. This work demonstrates that PICK1 plays a crucial role in the response to OGD that results in altered synaptic transmission and neuronal death and has implications for our understanding of the molecular mechanisms that underlie cell death during stroke.
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PMID:PICK1-mediated glutamate receptor subunit 2 (GluR2) trafficking contributes to cell death in oxygen/glucose-deprived hippocampal neurons. 1932 42

The ability to modify synaptic transmission between neurons is a fundamental process of the nervous system that is involved in development, learning, and disease. Thus, synaptic plasticity is the ability to bidirectionally modify transmission, where long-term potentiation and long-term depression (LTD) represent the best characterized forms of plasticity. In the hippocampus, two main forms of LTD coexist that are mediated by activation of either N-methyl-d-aspartic acid receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). Compared with NMDAR-LTD, mGluR-LTD is less well understood, but recent advances have started to delineate the underlying mechanisms. mGluR-LTD at CA3:CA1 synapses in the hippocampus can be induced either by synaptic stimulation or by bath application of the group I selective agonist (R,S)-3,5-dihydroxyphenylglycine. Multiple signaling mechanisms have been implicated in mGluR-LTD, illustrating the complexity of this form of plasticity. This review provides an overview of recent studies investigating the molecular mechanisms underlying hippocampal mGluR-LTD. It highlights the role of key molecular components and signaling pathways that are involved in the induction and expression of mGluR-LTD and considers how the different signaling pathways may work together to elicit a persistent reduction in synaptic transmission.
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PMID:Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms. 1992 78

Magnesium is a critical physiological ion, and magnesium deficiency might contribute to the development of pre-eclampsia, to impaired neonatal development and to metabolic problems extending into adult life. Pharmacologically, magnesium is a calcium antagonist with substantial vasodilator properties but without myocardial depression. Cardiac output usually increases following magnesium administration, compensating for the vasodilatation and minimising hypotension. Neurologically, the inhibition of calcium channels and antagonism of the N-methyl-d-aspartic acid (NMDA) receptor raises the possibility of neuronal protection, and magnesium administration to women with premature labour may decrease the incidence of cerebral palsy. It is the first-line anticonvulsant for the management of pre-eclampsia and eclampsia, and it should be administered to all patients with severe pre-eclampsia or eclampsia. Magnesium is a moderate tocolytic but the evidence for its effectiveness remains disputed. The side effects of magnesium therapy are generally mild but the major hazard of magnesium therapy is neuromuscular weakness.
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PMID:Magnesium in obstetrics. 2000 82

In the present study, the anti-stress effects of yeast hydrolysate (YH) were investigated. The YH consisted of crude carbohydrate (23.6%) and crude protein (68.3%) with low contents of crude ash (3.1%) and crude fat (0.3%). Also, acidic amino acids (glutamic acid + aspartic acid) were present in large quantities (14.2 and 5.0 mol%, respectively). Pronase digestion had little effect on the affinity of the YH on 5-hydroxytryptamine (serotonin) and norepinephrine transporters, whereas NaIO(4) oxidation of the hydrolysate decreased the affinity by about 10% at 1,000 microg/mL, indicating that the periodate-labile carbohydrate moiety played a leading role in the affinity effects of the carbohydrate in YH. As a result of brain mapping after the administration of the YH for 3 days in human subjects, a symmetrical distribution of theta and alpha waves in the central and parietal lobes was observed. This brain mapping pattern of theta and alpha wave distribution appears in a psychologically stable state. The YH groups showed improvements in Beck Depression Inventory and Beck Anxiety Inventory scores after YH administration for 2 weeks. Treatment also seemed to have a more significant (P < .05) impact on the somatic manifestations of anxiety as indexed by the Beck Anxiety Inventory scores. Food materials used as a source of YH have been found to be associated with increases in alertness and adaptation to stress.
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PMID:Chemical composition and anti-stress effects of yeast hydrolysate. 2004 82

Injecting a few mouse LD(50) of tetanus toxin into rat hippocampus has been shown to induce a remarkably persistent sequence of functional changes which provide a chronic model of limbic epilepsy. Here we have measured the release of amino acid transmitters evoked by K(+)-stimulation from hippocampal slices prepared from rats which had been injected 10-14 days previously with 6 mouse LD(50) (c. 3 ng) of tetanus toxin. The Ca(2+)-dependent component of the release of [(14)C]?-aminobutyric acid (GABA) was depressed to two thirds its control level. Rats which had survived 6-8 weeks, by which time the seizures had ceased, showed a recovery of the Ca(2+)-dependent component of the K(+)-evoked release of GABA to control levels, but these rats also exhibited a paradoxical depression of the Ca(2+)-independent component of release. [(3)H]d-Aspartate has previously been used as a putative marker for excitatory amino acid release. However, it failed to fulfil this role in the present study because its release was not stimulated by K(+). In contrast [(3)H]d-aspartate was released in response to veratrine. Together with previous work this suggests that while [(3)H]d-aspartate was taken up into neurones, it did not enter the releasable vesicular pool. HPLC measurements of the release of endogenous excitatory amino acids showed that glutamate (and not aspartate) was stimulated by K(+) in a Ca(2+)-dependent manner, and that the amount of release did not differ in the tetanus toxin-injected rats. The depression of GABA release provides the most likely mechanism for the seizures. The recovery of its Ca(2+)-dependent release provides the most likely basis for seizure remission after 6-8 weeks, in this chronic epileptic syndrome.
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PMID:Ex vivo release of GABA from tetanus toxin-induced chronic epileptic foci decreased during the active seizure phase. 2050 14

This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24-27 months) Sprague-Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3-5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N-Methyl-d-Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network.
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PMID:Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats. 2056 41


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