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

Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult (5-month-old) and aged (14-month-old) rats. Depression of levels of glutamine synthetase in the P2 fraction of kidney was observed, which was more severe in aged than young adult rats. Glutamine synthetase is a cytosolic enzyme especially susceptible to oxidative damage. A parallel depression of this enzyme was also seen in the corresponding hepatic fractions. However, levels of glutamine synthetase in the hippocampus were elevated by this exposure. Glutathione levels were depressed in P2 fractions of livers of exposed rats, and also in the corresponding renal fraction. Glutathione concentration was unchanged in cerebral fractions. Overall results were interpreted to imply that pro-oxidant events were elevated in kidney and liver following prolonged inhalation of the solvent mixture. The changes found in brain tissue did not reveal evidence of oxidative stress but, however, suggested that glial activation was taking place.
 ...
PMID:Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit. 749 80

Several biochemical parameters that reflect the presence of excess levels of reactive oxygen species were modulated in the brains of rats exposed acutely or subchronically to ethanol. These parameters included depression of cytosolic glutathione (GSH) concentration and of glutamine synthetase levels. However, using these indices, there was a significant difference in susceptibility to ethanol in different brain regions. After dietary exposure to ethanol for 12 days, these indices were selectively depressed in the striatum but not in the cerebral cortex or cerebellum. Eighteen hours after a single acute dose of ethanol (4.5 g/kg body wt), the striatum was also the only one of these areas in which proteolytic activity was elevated by ethanol treatment. Two injections of acetaldehyde (300 mg/kg), given 18 and 2 hr prior to tissue preparation, caused a specific reduction of glutamine synthetase in the striatum and a decrease of GSH levels in both striatum and cerebellum. Taken together, the results suggest a distinctive vulnerability of the striatum to ethanol-promoted oxidative events. Rather than ethanol exerting effects directly, the metabolite acetaldehyde may be the primary agent responsible for these changes.
 ...
PMID:Regional selectivity in ethanol-induced pro-oxidant events within the brain. 784 Jul 85

Rats were given a 200 mg/kg body weight daily dose of alpha-tocopherol by i.p. injection for 15 days. This resulted in elevated levels of glutathione in both liver and brain, and in a reduced hepatic rate of generation of reactive oxygen species. The depression of hepatic and cerebral glutathione levels in ethanol-consuming rats was prevented by simultaneous treatment with alpha-tocopherol. Other putative indices of hepatic pro-oxidant events, namely levels of mixed function oxidase and proteolytic activity, were elevated by alpha-tocopherol both in the presence and absence of ethanol. In addition, levels of enzymes especially susceptible to oxidative degradation, glutamine synthetase and creatine kinase, were depressed in the liver following treatment with ethanol or alpha-tocopherol. Parameters rapidly responsive to oxidative changes revealed the antioxidant property of alpha-tocopherol, while protein-based indices reflecting more extended events suggested a pro-oxidant effect of this vitamin. Results suggest that high levels of alpha-tocopherol can simultaneously lead to a more reduced intracellular environment and yet to localized evidence of enhanced oxidative events.
 ...
PMID:Prevention of ethanol-induced changes in reactive oxygen parameters by alpha-tocopherol. 887 90

Previous studies have demonstrated that cortical spreading depression (CSD) induces neuronal tolerance to a subsequent episode of ischemia. The objective of the present investigation was to determine whether CSD alters levels of mRNA coding for putative neuroprotective proteins. Unilateral CSD was evoked in male Wistar rats by applying 2 mol/L KCl over the frontal cortex for 2 hours. After recovery for 0, 2, or 24 hours, levels of several mRNA coding for neuroprotective proteins were measured bilaterally in parietal cortex using Northern blot analysis. Levels of c-fos mRNA and brain-derived neurotrophic factor (BDNF) mRNA were markedly elevated at 0 and 2 hours, but not 24 hours after CSD. Tissue plasminogen activator (tPA) mRNA levels were also significantly increased at 0 and 2 hours, but not 24 hours after CSD. Levels of the 72-kDa heat-shock protein (hsp72) mRNA were not significantly increased by CSD, except for a small elevation (20%) at 2 hours recovery. Levels of the 73-kDa heat-shock cognate (hsc73) mRNA were slightly, but significantly, increased at 2 and 24 hours of recovery. Finally, levels of mRNA for protease nexin-1 and glutamine synthetase were not significantly altered by CSD at any time studied. The current results support the hypothesis that neuronal tolerance to ischemia after CSD may be mediated by increased expression of FOS, BDNF, or tPA, but not by increased expression of hsp72, hsc73, nexin-1, or glutamine synthetase.
 ...
PMID:Effect of cortical spreading depression on the levels of mRNA coding for putative neuroprotective proteins in rat brain. 985 Jan 43

Aluminum lactate was injected either intraperitoneally or stereotactically into the lateral cerebral ventricles of rats. Rats were killed at various times after treatment, and frontal cortex, hippocampus, and striatum were dissected out. Microtiter plate-based sandwich ELISA and immunohistochemistry were used to measure the glial fibrillary acidic protein (GFAP) concentration. GFAP levels were significantly decreased in frontal cortex 7 days after a single lateral ventricular injection of aluminum lactate and 14 days following systemic treatment. In contrast, neither hippocampus nor striatum exhibited any significant changes in the content of this astrocytic intermediate filament protein after aluminum treatment. Levels of a predominantly astroglial enzyme, glutamine synthetase, were also selectively reduced in the frontal cortex following intraventricular injection of aluminum. This depression exhibited a regional and temporal specificity similar to that found for GFAP. These results suggest a selective and progressive diminution of astrocytic responsivity in frontal cortex following either systemic or intraventricular aluminum dosing. The depression of GFAP levels reported here, which was found in the rat cerebral cortex 7-14 days after aluminum treatment in a species that does not form neurofilamentous aggregates, may reflect extended impairment of astrocytic function and suggests that these cells may be the primary targets of aluminum neurotoxicity.
 ...
PMID:Decrease of glial fibrillary acidic protein in rat frontal cortex following aluminum treatment. 1050 Dec 7

The filamentous non-heterocystous cyanobacterium Plectonema boryanum fixes dinitrogen at a high rate during microaerobic growth in continuous illumination by temporal separation of oxygen-evolving photosynthesis and oxygen-sensitive dinitrogen fixation. The onset of nitrogen fixation is preceded by a depression in photosynthesis that establishes a sufficiently low level of dissolved oxygen in the growth medium. A several-fold reduction in the level of transcripts coding for phycocyanin (cpcBA) and the chlorophyll a binding protein of photosystem II (psbC) and psbA accompanied the depression in photosynthetic oxygen evolution. Unlike most of the other organisms examined to date, in P. boryanum, psbC and psbD do not appear to be co-transcribed. The psbC transcripts were down-regulated several fold, while the psbD transcript declined marginally during the nitrogen fixation phase. A decrease in dissolved oxygen and a dramatic increase in the level of nifH transcripts and the enzyme activity of nitrogenase were characteristic of the nitrogen fixation phase. The level of transcript for glnA, which encodes glutamine synthetase, was not altered. Reciprocal regulation of gene expression was well orchestrated with the alternating cycles of photosynthesis and nitrogen fixation in P. boryanum.
 ...
PMID:Differential expression of photosynthesis and nitrogen fixation genes in the cyanobacterium Plectonema boryanum. 1071 36

Elevated levels of aluminium (Al), strontium (Sr), barium (Ba), iron (Fe), manganese (Mn) cations - combined with deficiencies of magnesium (Mg)/calcium (Ca) - have been observed in the foodchains that traditionally support the Chamorro populations affected by high incidence clusters of Alzheimer (AD), Parkinson-like (PD), motor neurone diseases and multiple sclerosis on the island of Guam. Soils drawn from the cluster region demonstrated an excessive fivefold increase in 'magnetic susceptibility' readings in relation to soils from disease free adjoining regions. A multifactorial aetiological hypothesis is proposed that pivots upon the combined exposure to high levels of natural/industrial sources of ferrimagnetic/ferroelectric compounds incorporating Al, Fe, Mn, Sr, Ba (e.g., via yam/seafood consumption or exposure to world war 2 (WW2) munitions) and to low levels of Mg/Ca in all S. Pacific locations where these clusters of neurodegenerative disease have simultaneously erupted. Once gut/blood brain barrier permeability is impaired, the increased uptake of Al, Fe, Sr, Ba, or Mn into the Mg/Ca depleted brain leads to rogue metal substitutions at the Mg/Ca vacated binding domains on various enzyme/proteoglycan groups, causing a broad ranging disruption in Mg/Ca dependent systems - such as the glutamine synthetase which prevents the accumulation of neurotoxic glutamate. The rogue metals chelate sulphate, disrupting sulphated-proteoglycan mediated inhibition of crystal proliferation, as well as its regulation of the Fibroblast growth factor receptor complex which disturbs the molecular conformation of those receptors and their regulation of transphosphorylation between intracellular kinase domains; ultimately collapsing proteoglycan mediated cell-cell signalling pathways which maintain the growth and structural integrity of the neuronal networks. The depression of Mg/Ca dependent systems in conjunction with the progressive ferrimagnetisation of the CNS due to an overload of rogue ferroelectric/ferrimagnetic metal contaminants, enables 'seeding' of metal-protein crystalline arrays that can proliferate in the proteoglycan depleted brain. The resulting magnetic field emissions initiate a free radical mediated progressive pathogenesis of neurodegeneration. The co-clustering of these various types of disease in select geographical pockets around the world suggests that all of these conditions share a common early life exposure to ferromagnetic metal nucleating agents in their multifactorial aetiology. Factors such as individual genetics, the species of metal involved, etc., dictate which specific class of disease will emerge as a delayed neurotoxic response to these environmental insults.
 ...
PMID:Elevated levels of ferrimagnetic metals in foodchains supporting the Guam cluster of neurodegeneration: do metal nucleated crystal contaminants [corrected] evoke magnetic fields that initiate the progressive pathogenesis of neurodegeneration? 1548 50

Abnormalities in L-glutamic acid (glutamate) and GABA signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular determinants and neural mechanisms. Microarray analysis of specific areas of cerebral cortex from individuals who had suffered from major depressive disorder demonstrated significant down-regulation of SLC1A2 and SLC1A3, two key members of the glutamate/neutral amino acid transporter protein family, SLC1. Similarly, expression of L-glutamate-ammonia ligase, the enzyme that converts glutamate to nontoxic glutamine was significantly decreased. Together, these changes could elevate levels of extracellular glutamate considerably, which is potentially neurotoxic and can affect the efficiency of glutamate signaling. The astroglial distribution of the two glutamate transporters and L-glutamate-ammonia ligase strongly links glia to the pathophysiology of depression and challenges the conventional notion that depression is solely a neuronal disorder. The same cortical areas displayed concomitant up-regulation of several glutamate and GABA(A) receptor subunits, of which GABA(A)alpha1 and GABA(A)beta3 showed selectivity for individuals who had died by suicide, indicating their potential utility as biomarkers of suicidality. These findings point to previously undiscovered molecular underpinnings of the pathophysiology of major depression and offer potentially new pharmacological targets for treating depression.
 ...
PMID:Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. 1623 Jun 5

Cowpea Bradyrhizobium 32H1 cells, when grown under 0.2% O(2), synthesize nitrogenase, as well as a methylammonium (ammonium) transport system and an electrogenic K(+)/H(+) antiporter. This effect was seen in growth medium containing 8-12 mM K(+) but not with 50 muM K(+). Addition of K(+) to cells growing under low O(2) tensions in low-K(+) medium led to various phenotypic properties associated with bacteroids, including the ability to reduce acetylene, induction of an ammonium transport carrier and the K(+)/H(+) antiporter, and increased synthesis of two heme-biosynthetic enzymes, delta-aminolevulinate synthase and delta-aminolevulinate dehydratase. K(+) addition caused the repression of glutamine synthetase and of capsular polysaccharide synthesis, functions related to the free-living state. A similar pattern of regulation was observed in Bradyrhizobium japonicum. In addition, K(+)-mediated depression in Bradyrhizobium 32H1 was inhibited by exudate of Vigna unguiculata, its host plant. We conclude that K(+) ions, in addition to low O(2) tension, are needed for the expression of several bacteroid-related functions in bradyrhizobia and thus are a major controlling influence in bacteroid development.
 ...
PMID:K regulates bacteroid-associated functions of Bradyrhizobium. 1659 58

Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment-resistant depression. Despite the efficacy of electroconvulsive seizure as a non-chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20-30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation-3. There was also an induction of the angiogenesis markers alphaVbeta3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.
 ...
PMID:Electroconvulsive seizure increases adult hippocampal angiogenesis in rats. 1693 Apr 11


<< Previous 1 2 3 4 Next >>