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)

This paper provides evidence that it is possible to prepare facilitating anti-mouse immunoglobulin (that is, anti-mouse immunoglobulin which facilitates complementary lysis of red cells sensitized with mouse-produced haemolysin) which, when injected into mice 24 hours before an injection of sheep red cells, very markedly reduced the number of haemolysin-producing cells detectable in spleen four days later. The diffusion-lysis method was used to recognize this and other anti-Ig's in heterologous antiserum and fractions thereof. The effective antibody was in the gamma2 fraction of antiserum produced in guinea pigs by injecting them with guinea pig red cells sensitized with mouse-produced haemolysin. This method of immunizing was used in order to stimulate the production of antibody against immunoglobulin which had undergone the configurational change characteristically occurring when antibody unites with antigen. The 19S fraction of the antiserum contained inhibiting anti-mouse immunoglobulin (anti-mouse immunoglobulin which inhibits complementary lysis of red cells sensitized with mouse-produced haemolysin) and interfered with immune depression by the gamma2 fraction. It is postulated that the gamma2 fraction induces complementary lysis only of lymphocytes whose surface immunoglobulin receptors have bound antigen and undergone configurational change. It is suggested that facilitating anti-immunoglobulin of the type described is responsible for immune suppression by anti-lymphocyte serum (ALS). Facilitating anti-mouse immunoglobulin was demonstrated in two samples of ALS (anti-mouse) which were active in suppressing graft rejection, but inhibiting anti-mouse immunoglobulin only was found in a sample which was ineffective in suppressing graft rejection.
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PMID:Anti-immunoglobulin analysis by diffusion patterns of inhibition and facilitation of complementary lysis in agar. II. Diffusion-lysis as a method for recognizing in vivo immunosuppressive activity of anti-immunoglobulins. 80 24

The gamma-aminobutyric acid type A (GABAA) receptor is a transmitter-gated ion channel mediating the majority of fast inhibitory synaptic transmission within the brain. The receptor is a pentameric assembly of subunits drawn from multiple classes (alpha1-6, beta1-3, gamma1-3, delta1, and epsilon1). Positive allosteric modulation of GABAA receptor activity by general anesthetics represents one logical mechanism for central nervous system depression. The ability of the intravenous general anesthetic etomidate to modulate and activate GABAA receptors is uniquely dependent upon the beta subunit subtype present within the receptor. Receptors containing beta2- or beta3-, but not beta1 subunits, are highly sensitive to the agent. Here, chimeric beta1/beta2 subunits coexpressed in Xenopus laevis oocytes with human alpha6 and gamma2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate. The mutation of an amino acid (Asn-289) present within the channel domain of the beta3 subunit to Ser (the homologous residue in beta1), strongly suppressed the GABA-modulatory and GABA-mimetic effects of etomidate. The replacement of the beta1 subunit Ser-290 by Asn produced the converse effect. When applied intracellularly to mouse L(tk-) cells stably expressing the alpha6beta3gamma2 subunit combination, etomidate was inert. Hence, the effects of a clinically utilized general anesthetic upon a physiologically relevant target protein are dramatically influenced by a single amino acid. Together with the lack of effect of intracellular etomidate, the data argue against a unitary, lipid-based theory of anesthesia.
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PMID:The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid. 938 Jul 54

The P/Q type voltage-gated Ca2+ channels are involved in membrane excitability and Ca2+-dependent neurotransmitter release within the CNS. Mutations in the CacnalA gene encoding the alpha1A subunit of the P/Q type Ca2+ channel have recently been reported in tottering mice and a more severely affected allele, leaner. Here we show using in vivo cortical microdialysis that evoked increases of extracellular glutamate levels are markedly attenuated in both mutants upon KCl-induced depolarization compared with wild-type mice. Tottering and leaner mice also show a 10-fold resistance to cortical spreading depression induced by cortical electrical stimulation or KCl application to the pial surface. A slower transcortical propagation speed and failure to sustain regenerative spread of the depolarizing wave were more pronounced in leaner neocortex. Both signaling defects appeared unrelated to the developmental history of repeated cortical spike-wave discharges, since neither were observed in the stargazer mouse, a Ca2+ channel gamma2 subunit mutant with a similar seizure phenotype. These data demonstrate two cortical excitability defects revealed by prolonged depolarization in cerebral networks expressing mutant P/Q type Ca2+ channels, and are the first to identify a gene linked to a spreading depression phenotype.
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PMID:Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels. 1067 Apr 32

Pharmacological evidence suggests the involvement of gamma-aminobutyric acid (GABA) perturbation in the etiology of mood disorders. A linkage study has detected chromosomal area 5q34, where GABA type A (GABA(A)) receptor subunit genes are mapped, as a susceptibility region for mood disorders, making these genes compelling candidates for such diseases. Our prior quantitative trait loci (QTL) analysis of mouse depression models identified a QTL on mouse chromosome 11, a genomic region whose human synteny includes 5q34. This further supports a contribution from GABA(A) receptors to a predisposition towards mood disorder. In the present study, we examined GABA(A) receptor alpha1 (GABRA1), alpha6 (GABRA6) and gamma2 (GABRG2) subunit genes on 5q34. Polymorphisms on GABRA1 and GABRA6 genes displayed significant associations with mood disorders in female patients. These data offer genetic support for a role of GABA(A) receptor genes in susceptibility to mood disorders.
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PMID:Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders. 1294 74

Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH1, and CRH2 receptors, as well as various GABA(A) receptor subunits (alpha1, alpha2, alpha3, alpha4, alpha5, delta, and gamma2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the alpha1, alpha3, alpha4, and delta receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABA(A) receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABA(A) receptor subunit changes, or the disturbed coordination between these GABA(A) receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.
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PMID:Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. 1496 Jun 21

Chronic stress causes disinhibition of the hypothalamus-pituitary-adrenal axis. Consequently, the brain is overexposed to glucocorticoids which in humans may precipitate stress-related disorders, e.g. depression. The hypothalamus-pituitary-adrenal activity is strongly regulated by GABAergic input to parvocellular neurons in the hypothalamic paraventricular nucleus. We here report a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) in parvocellular neurons of rats exposed to 3 weeks of unpredictable stress. The mIPSC amplitude and kinetic properties were unchanged, pointing to a presynaptic change caused by chronic stress. Because paired-pulse inhibition was unaffected by chronic stress, the number of functional GABAergic synaptic contacts rather than the release probability seems to be reduced after chronic stress. Linearly amplified RNA from postsynaptic cells was hybridized with multiple cDNA clones of interest, including most GABA(A) receptor subunits. In agreement with the electrophysiological observations, relative expression of the prevalent GABA(A)alpha1, alpha3, gamma1 and gamma2 receptor subunits, which largely contribute to the recorded responses, was not altered after chronic stress. However, expression of the extra-synaptic GABA(A)alpha5 subunit, earlier linked to depression in humans, and of the delta receptor subunit were found to be significantly changed. In conclusion, chronic stress leads to presynaptic functional alterations in GABAergic input to the paraventricular nucleus which could contribute to the observed disinhibition of the hypothalamus-pituitary-adrenal axis; additionally other aspects of GABAergic transmission may also be changed due to transcriptional regulation of specific receptor subunits in the parvocellular neurons.
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PMID:Chronic stress attenuates GABAergic inhibition and alters gene expression of parvocellular neurons in rat hypothalamus. 1535 34

Data on the effects of Plasmodium gallinaceum on domesticated fowl are sparse, justifying a full investigation of its pathology. Clinical signs following blood-induced infections with the Wellcome line of strain 8A included depression, fever, anorexia, reduced weight gain, poor feed conversion, anaemia, green faeces and often death. After administration of 10(6) erythrocytic parasites, mortality 5 to 10 days after infection was 10% to 93% in chickens 7 to 84 days old. The older the birds, the lower the mortality and the longer the time to death. Onset of detectable parasitaemia occurred mostly during the second day after infection (59% of birds). Peak parasitaemia (approximately 70%) occurred on the sixth day in 85% of surviving birds. The patent period was usually 7 to 19 days. Abnormally low haematocrit values of < or =24% and high colonic temperatures of > or =42 degrees C were recorded. A febrile response is demonstrated conclusively here in P. gallinaceum malaria for the first time. Weight gain of malarious birds was reduced by approximately 18% to 51%, and feed conversion efficiency was often reduced by approximately 12% to 41%. Growth reduction was due entirely to anorexia. Liver weight relative to body weight (normally approximately 2% to 3%) increased to approximately 4.5% by 8 days, and relative spleen weight (normally approximately 0.2%) increased to 1.6% by 12 days. Specific gravities of livers and spleens in healthy and infected birds were approximately 1.09. Gall bladder volume in malarious birds 8 days after infection was approximately four times that of normal birds. Statistically significant changes occurred in the proportions of plasma proteins in malarious birds 8 days after infection; albumin and alpha2-globulin were reduced, while gamma1-globulin and gamma2-globulin were increased. Those changes coincided with significant increases in concentrations of plasma total protein and the enzymes aspartate aminotransferase, glutamate dehydrogenase and gamma-glutamyltransferase, and a decrease in creatinine. Green (biliverdin) colouration of the faeces was a consistent sign of malaria. Birds acquired non-sterile immunity after a single primary infection. The quantitative data presented facilitate selection of the most useful criteria for field diagnosis, estimation of potential economic losses, and assessment of potential avian antimalarial drugs.
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PMID:Avian malaria: clinical and chemical pathology of Plasmodium gallinaceum in the domesticated fowl Gallus gallus. 1576 37

A spreading depression (SD) can spontaneously develop in seizures, attacks of migraine, vascular disorders and other pathological states of the brain. However, problems in technique of recording the DC-potential in the neocortex of humans and waking animals substantially restrict the possibilities of studying functional consequences of the SD. In this article, the EEG pattern was studied in detail at the moment of the SD development. Specific features were revealed, which make it possible to detect the SD without recording shifts of the DC-potential. At the moment of the SD arrival, the interhemispheric balance drastically disturbs because of a strong decrease in the high-frequency activity. By the time indices, the course of the suppression of the gammal and gamma2 EEG frequencies is the most reliable symptom of the SD wave development. The EEG spectral power in the delta band increases with a certain delay in reference to the deep depression of the high-frequency activity and is, in essence, an SD aftereffect. The found EEG signs of an SD wave can substantially simplify the identification of this phenomenon both in experiment and clinical conditions in certain pathological states of the brain.
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PMID:[Suppression of gamma EEG activity as an index of a spreading depression wave in the neocortex of a waking rabbit]. 1621 57

Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and depression, which suggests a dysfunction of GABAergic neurotransmission. Socially isolated female mice that have received testosterone propionate (1.45 micromol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2 are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5-hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level downregulation and abolishes aggression. This work underscores the role of neurosteroids in the regulation of aggression elicited by testosterone propionate in socially isolated female mice.
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PMID:Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids. 1695 4

Protracted social isolation in laboratory animals causes stress, which induces a variety of behavioral abnormalities including increased aggressiveness, anxiety-related behaviors, cognitive deficits and hyper locomotion. Many of these disorders are similar to the symptoms found in psychiatric disorders, such as depression, anxiety, premenstrual dysphoria and posttraumatic stress disorders (PTSD). Recent studies have demonstrated that male mice that have been socially isolated for more than 4 weeks show: (a) reduced responsiveness of GABA(A) receptors (GABA(A)-R) to the administrations of GABA mimetic drugs at GABA(A)-R; (b) downregulated biosynthesis of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) (allopregnanolone: ALLO), a neurosteroid with a potent positive allosteric modulatory effect on the action of GABA on GABA(A)-R; and (c) alterations in the expression of GABA(A)-R subunits (i.e. a decrease of alpha1/alpha2 and gamma2 subunits and an increase of alpha4 and alpha5 subunits). The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) and its congener norfluoxetine (Nor-FLX), when administered systemically at nmol/kg doses, normalize the reduced content of brain ALLO and the reduced responsiveness of GABA(A)-R to GABA mimetic drugs (i.e. pentobarbital) and also attenuate aggressive behavior in socially isolated mice in a stereospecific manner. Although these compounds inhibit ex vivo serotonin reuptake into brain tissue, their SSRI activities require high micromol/kg dose ranges and are not stereospecific. These studies suggest that in socially isolated mice, abnormalities of GABA(A)-R signal transduction are attributable to the downregulation of ALLO production and to a switch in heteropentameric GABA(A)-R subunit assembly composition. Hence, the normalization of ALLO biosynthesis may be a new target for the development of drugs effective for psychiatric disorders related to neurosteroid biosynthesis downregulation.
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PMID:GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. 1745 62


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