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)

Neurosteroids (NS) are steroids synthesized by the brain. Neuroactive steroids (NAS) refers to steroids that, independent of their origin, are capable of modifying neural activities. NAS bind and modulate different types of membrane receptors. The gamma amino butyric acid (GABA) and sigma receptor complexes have been the most extensively studied. Oxidized ring A reduced pregnanes, tetrahydroprogesterone (THP), and tetrahydrodeoxycorticosterone (THDOC) bind to the progesterone intracellular receptor (PR), and in this way can also regulate gene expression. Animal experimentation showed that salient symptoms of depression, viz., anxiety, sleep disturbances, and memory and sexual dysfunctions, are modulated by NAS. In turn, psychotropic drugs modulate NS and NAS levels. NS levels as well as NAS plasma concentrations change in patients with depression syndromes, the levels return to normal baseline with recovery, but normalization is not necessary for successful therapy. Results from current studies on the evolution of nervous systems, including evolutionary developmental biology as well as anatomical and physiological findings, almost preclude a categorical classification of the psychiatric ailments the human brain succumbs to. The persistence in maintaining such essentialist classifications may help to explain why up to now the search for biological markers in psychiatry has been an unrewarding effort. It is proposed that it would be more fruitful to focus on relationships between NAS and symptoms of psychiatric disorders, rather than with typologically defined disorders.
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PMID:Neurosteroids, neuroactive steroids, and symptoms of affective disorders. 1696 51

Thyroid hormones are necessary for brain development. gamma-Amino-butyric acid (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in brain, many of which contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe postnatal hypothyroidism reduces PV immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal serum T(4) by approximately 50-75% and increased TSH. At weaning, T(4) was reduced by approximately 70% in offspring in the low-dose group and fell below detectable levels in high-dose animals. PV-IR was diminished in the hippocampus and neocortex of offspring killed on postnatal d 21, an effect that could be reversed by postnatal administration of T(4). Dose-dependent decreases in the density of PV-IR neurons were observed in neocortex and hippocampus, with the dentate gyrus showing the most severe reductions (50-75% below control counts). Altered staining persisted to adulthood despite the return of thyroid hormones to control levels. Developmental cross-fostering and adult-onset deprivation studies revealed that early postnatal hormone insufficiency was required for an alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions in paired pulse depression indicative of a suppression of GABA-mediated inhibition. These data demonstrate that moderate degrees of thyroid hormone insufficiency during the early postnatal period permanently alters interneuron expression of PV and compromises inhibitory function in the hippocampus.
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PMID:Thyroid hormone insufficiency during brain development reduces parvalbumin immunoreactivity and inhibitory function in the hippocampus. 1700 98

Modafinil (2-[(Diphenylmethyl) sulfinyl] acetamide, Provigil) is an FDA-approved medication with wake-promoting properties. Pre-clinical studies of modafinil suggest a complex profile of neurochemical and behavioral effects, distinct from those of amphetamine. In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia. Cognitive dysfunction may be a particularly important emerging treatment target for modafinil, across these and other neuropsychiatric disorders. We aimed to comprehensively review the empirical literature on neurochemical actions of modafinil, and effects on cognition in animal models, healthy adult humans, and clinical populations. We searched PubMed with the search term 'modafinil' and reviewed all English-language articles for neurochemical, neurophysiological, cognitive, or information-processing experimental measures. We additionally summarized the pharmacokinetic profile of modafinil and clinical efficacy in psychiatric patients. Modafinil exhibits robust effects on catecholamines, serotonin, glutamate, gamma amino-butyric acid, orexin, and histamine systems in the brain. Many of these effects may be secondary to catecholamine effects, with some selectivity for cortical over subcortical sites of action. In addition, modafinil (at well-tolerated doses) improves function in several cognitive domains, including working memory and episodic memory, and other processes dependent on prefrontal cortex and cognitive control. These effects are observed in rodents, healthy adults, and across several psychiatric disorders. Furthermore, modafinil appears to be well-tolerated, with a low rate of adverse events and a low liability to abuse. Modafinil has a number of neurochemical actions in the brain, which may be related to primary effects on catecholaminergic systems. These effects are in general advantageous for cognitive processes. Overall, modafinil is an excellent candidate agent for remediation of cognitive dysfunction in neuropsychiatric disorders.
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PMID:Modafinil: a review of neurochemical actions and effects on cognition. 1771 50

Sodium butyrate (NaB), a histone deacetylase inhibitor, has been implicated in the antidepressant-like effects either injected as a single drug or in combination with selective serotonin reuptake inhibitor (SSRI), such as fluoxetine. Estrogen is also demonstrated to have antidepressant effect especially together with fluoxetine. We investigated whether NaB administered in combination with estradiol benzoate (EB) exerted antidepressant-like effect in forced swimming test (FST) in ovariectomized female rats. Furthermore, we detected the mRNA expressions of serotonin receptors and neuropeptides in hypothalamus, both of which participate in the mood disorder. Ovariectomized female SD rats were treated with vehicle, NaB, EB or NaB combined with EB for 7 days and then subjected to FST. The expressions of serotonin receptors (5-hydroxytryptamine receptor), corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the hypothalamus were detected by real time PCR. We found that co-treated with NaB and EB resulted in a significant decrease in immobility behavior in FST, a measure for depression-like behavioral. 5-HT(1A) antagonist, WAY 100635, significantly block the antidepressant-like effects induced by NaB plus EB. The mRNA expression of the serotonin-1A [5-hydroxytryptamine 1A (5-HT(1A))] receptor was increased in the co-treated group in hypothalamus, while there was no difference in the mRNA expression of 5-HT(2A) or 5-HT(2C). The mRNA expression of CRH or AVP was not significantly altered either. In conclusion, NaB may exert antidepressant-like effects in combination with EB in ovariectomized female rats through 5-HT(1A) receptor, via altering the expression of 5-HT(1A) in the hypothalamus.
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PMID:Antidepressant-like effects of sodium butyrate in combination with estrogen in rat forced swimming test: involvement of 5-HT(1A) receptors. 1881 16

The present study was carried out to evaluate the biological properties of the tissue extract of a marine snail Telescopium telescopium, collected from the coastal regions of West Bengal India. On extensive pharmacological screening, it was found that the biological extract of T. telescopium (TTE) produced significant central nervous system (CNS)-depressant activity as observed from the reduced spontaneous motility, potentiation of pentobarbitone induced sleeping time, hypothermia and respiratory depression with transient apnoea. The extract significantly decreased both residual curiosity and also muscle coordination. The fraction, obtained following saturation with 60-80% ammonium sulphate (80S), was also found to demonstrate predominant CNS-depressant activity. It was observed that both TTE and the 80S fraction significantly altered the brain noradrenaline and homovanillic acid levels without affecting the brain gamma amino butyric acid (GABA) concentration. Based on the present observations, it can be suggested that the CNS-depressant effects produced by TTE and 80S could be attributable to modified catecholamine metabolism in the brain.
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PMID:An insight on the neuropharmacological activity of Telescopium telescopium--a mollusc from the Sunderban mangrove. 1904 73

1. The effect of potassium diformate (KDF) on mortality, growth performance, microbial populations, pH and short chain fatty acid concentrations in the intestinal tract of broiler chickens challenged with necrotic enteritis was investigated. 2. An experiment with 1050 Cobb male broiler chickens was conducted from 1 to 35 d of age. There were 7 treatment groups: (1) unchallenged negative control, (2) unchallenged KDF (4.50 g/kg feed), (3) challenged negative control, (4) challenged positive control (100 ppm monensin and 45 ppm Zn-bacitracin), and (5) to (7) challenged KDF (inclusion rate 2.25, 4.50 and 6.75 g/kg feed, respectively). 3. The necrotic enteritis challenge caused significant growth depression except in the challenged positive control group. Inclusion of KDF in feed had no significant effect on weight gain or feed conversion ratio, neither under challenged nor unchallenged conditions. Necrotic-enteritis-related mortalities were reduced in response to the positive control feed and KDF at 2.25 and 4.50 g/kg rates, but with no effect at the 6.75 g/kg rate. 4. There was no effect of KDF on Clostridium perfringens numbers in jejunum during the necrotic enteritis challenge (d 15). Post challenge (d 35), 4.5 g/kg KDF reduced the number of C. perfringens and Enterobacteria in jejunum compared with the negative control group. 5. Intestinal pH was not affected by adding KDF to the feed. The challenge reduced jejunum pH compared with the unchallenged treatment groups and challenged positive control group. 6. Chickens fed the KDF diets had detectable concentrations of formic acid in the jejunum. There was a tendency towards higher concentrations of acetic acid and lactic acid in the small intestine of unchallenged birds, whereas challenged birds had higher concentrations of butyric acid in the caeca. 7. It is concluded that KDF holds promise as an agent to control necrotic enteritis in broiler chickens and it may be possible to enhance the efficacy of KDF by manipulating dietary properties that may influence the dissociation kinetics of KDF in the gut.
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PMID:Effect of potassium diformate on growth performance and gut microbiota in broiler chickens challenged with necrotic enteritis. 1923 31

1. Under certain conditions, general autolysis does not begin immediately upon the removal of the organ from its circulation. This latent period is more apt to be present in those cases in which the tissues have been temporarily cooled on account of the use of a cold saline diluent or in which the percentage concentration of the inorganic salts (calcium or potassium), of the tissues have been changed by dilution with a sodium chloride solution. The presence of blood and absence of fats and of glycogen in the cells act as important factors in prolonging the latent period. 2. Attempts to produce an alkaline reaction (phenolphthalein) in the tissue resulted negatively. Solutions of disodium hydrogen phosphate and of sodium bicarbonate when added to the liver tissues gave a mixture which was acid to phenolphthalein and had no apparent effect upon autolysis. 3. The addition of antiseptics-chloroform and toluol-markedly decreased the rate of autolysis. Ordinary light produced no effect. 4. Ethyl butyrate when added to the tissue became hydrolysed into butyric acid; the formation of this acid in the mixture caused a decided acceleration in the autolytic rate. The acidity of a solution of dihydrogen sodium phosphate failed to produce a similar result. 5. The figures for the changes in the depression of the freezing-point, non-coaguable nitrogen and reaction of the autolytic mixture do not parallel one another. In some experiments a marked increase in the depression of the freezing-point was unaccompanied by augmentation of non-coagulable nitrogen. 6. General autolysis is the sum total of proteolytic, amylolytic and lipolytic factors. Each of these autolytic factors may proceed alone for a time; the rate of one is decidedly influenced by the presence or absence of the others. The acid products which are the result of amylolytic (lactic acid) and of lipolytic (higher fatty acids) autolysis, exert a pronounced augmentative effect upon the commencement and rate of nitrogenous autolysis.
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PMID:THE EFFECT OF CONDITIONS UPON THE LATENT PERIOD AND RATE OF ASEPTIC POST MORTEM AUTOLYSIS DURING THE FIRST TEN HOURS. 1986 44

1. Exposure of unfertilized starfish eggs to dilute solutions of weak acids (fatty acids, benzoic and carbonic acids) in isotonic balanced salt solution causes complete activation with the proper durations of exposure. For each acid the rate of activation (reciprocal of optimum duration) varies with concentration and temperature; at a given temperature and within a considerable range of concentrations (e.g. 0.00075 to 0.004 M for butyric acid), this rate is approximately proportional to concentration. We may thus speak of a molecular rate of action characteristic of each acid. 2. In general the molecular rate of action increases with the dissociation constant and surface activity of the acids. In the fatty acid series (up to caproic), formic acid has the most rapid effect, acting about four times as rapidly as acetic; for the other acids the order is: acetic = propionic <== butyric < valeric < caproic. Carbonic acid acts qualitatively like the fatty acids, but its molecular rate of action is only about one-fourteenth that of acetic acid. 3. Hydrochloric and lactic acids are relatively ineffective as activating agents, apparently because of difficulty of penetration. Lactic acid is decidedly the more effective. The action of both acids is only slightly modified by dissolving in pure (isotonic NaCl and CaCl(2)) instead of in balanced salt solution. 4. The rate of action of acetic acid, in concentrations of 0.002 M to 0.004 M is increased (by 10 to 20 per cent) by adding Na-acetate (0.002 to 0.016) to the solution. The degree of acceleration is closely proportional to the estimated increase in undissociated acetic acid molecules. Activation thus appears to be an effect of the undissociated acid molecules in the external solution and not of the ions. Acetate anions and H ions acting by themselves, in concentrations much higher than those of the solutions used, have no activating effect. The indications are that the undissociated molecules penetrate rapidly, the ions slowly. Having penetrated, the molecules dissociate inside the egg, yielding the ions of the acid. 5. When the rate of activation is slow, as in 0.001 M acetic acid, the addition of Na-acetate (0,008 M to 0.016 M) has a retarding effect, referable apparently to the gradual penetration of acetate ions to the site of the activation reaction with consequent depression of dissociation. 6. An estimate of the C(H) of those solutions (of the different activating acids) which activate the egg at the same rate indicates that their H ion concentrations are approximately equal. On the assumptions that only the undissociated molecules penetrate readily, and that the conditions of dissociation are similar inside and outside the egg, this result indicates (especially when the differences in adsorption of the acids are considered) that the rate of activation is determined by the C(H) at the site of the activation reaction within the egg.
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PMID:THE ACTIVATION OF STARFISH EGGS BY ACIDS. 1987 5

The present study aimed to investigate olfactory anhedonia and olfactory negative alliesthesia in depressed patients. Two odorants, one with pleasant (vanillin), and one with unpleasant (butyric acid) hedonic valence were evaluated by 30 depressed inpatients and 30 controls (healthy subjects, matched by age and gender). Participants explored the hedonic valence, intensity (discrimination) and perceived quality (identification) of 16 different stimuli (3 concentrations of odorants, their 9 combinations, and 1 control containing distilled water). The hedonic perception showed that patients perceived the unpleasant odorant as significantly more unpleasant than controls (olfactory negative alliesthesia). Concerning the intensity ratings, controls were able to discriminate between all concentrations of odorants, while patients discriminated between the different concentrations only for the unpleasant component and not for the vanillin (olfactory anhedonia). Regarding the identification task in an iso-intense unmixed odorants mixture, patients perceived significantly less the pleasant odorant than the unpleasant one (olfactory anhedonia), whereas controls perceived both odorants equally well. These results support the notion of an olfactory perception impairment in depression. Further studies are needed to replicate these findings and to confirm that such olfactory anhedonia or/and olfactory negative alliesthesia could be a state or a trait of depression.
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PMID:Olfactory anhedonia and negative olfactory alliesthesia in depressed patients. 2020 22

gamma-Amino butyric acid is an extremely important inhibitory neurotransmitter in the mammalian central nervous system and is essential for the overall balance between neuronal excitation and inhibition. It is well documented that GABA deficiency is associated with several important neurological disorders such as Huntington's chorea, Parkinson's and Alzheimer's disease and other psychiatric disorders, like anxiety, depression, pain, panic, or mania. Although, it is known that increasing the brain concentration of GABA prevents convulsions, the high polarity and flexible structure of this compound are probably responsible for its inefficiency as an anticonvulsant when administered orally or intravenously. To resolve this problem, GABA analogues are being designed. Over recent years, there has been increasing interest in the synthesis and pharmacological effect of new GABA derivatives, which can be considered as potent drugs in the treatment of neurodegenerative disorders.
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PMID:A role of GABA analogues in the treatment of neurological diseases. 2049 40


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