Regulation of DREAM Expression by Group I mGluR

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.

Roles of Metabotropic Glutamate Receptors 1 and 5 in Rat Medial Vestibular Nucleus Neurons

Using whole cell current- and voltage-clamp recording we investigated the characteristics and pharmacology of group I metabotropic glutamate receptor (mGluR)-mediated responses in rat medial vestibular nucleus (MVN) neurons. In current clamp conditions, activation of mGluR I by application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced a direct excitation of MVN neurons that is characterized by depolarization and increased spontaneous firing frequency. To identify which of mGluR subtypes are responsible for the various actions of DHPG in MVN, we used two subtype-selective antagonists. (S)-(+)-alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. In voltage clamp conditions, DHPG application increased the frequency of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) but had no effect on amplitude distributions. Antagonism of the DHPG-induced increase of miniature IPSCs required the blockade of both mGluR1 and mGluR5. DHPG application induced an inward current, which can be enhanced under depolarized conditions. DHPG-induced current was blocked by LY367385, but not by MPEP. Both LY367385 and MPEP antagonized the DHPG-induced suppression of the calcium activated potassium current (IAHP). These data suggest that mGluR1 and mGluR5 have similar roles in the regulation of the excitability of MVN neurons, and show a little distinct. Furthermore, mGluR I, via pre- and postsynaptic actions, have the potential to modulate the functions of the MVN.

Effect of folic acid administration on plasma level of methoxy hydroxy phenyl glycol in perimenopausal women

The need for a nonhormonal approach to the treatment of subjective symptoms of menopause is evident. The present study aimed to test the effectiveness of folic acid in eliminating postmenopausal hot flushes and its effect on the related noradrenaline metabolite, 3- methoxy 4-hydnoxy phenyl glycol [MHPG] plasma level. also, its effect on the lipid profile including serum triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and C-reactive protein [CRP] were studied. Sixty-four menopausal women complaining of hot flushes were included into 3 groups: group I [23 menopausal women] received folic acid 5 mg tablets once daily, group 11[22 menopausal women] received folic acid 5 mg tablet twice daily and group III [19 menopausal women] received placebo tablets once daily, for 4 weeks. The women were followed up as regards the frequency of hot flushes and estimation of plasma level of MHPG by high performance liquid chromatography [HPLC], serum lipid profile and CRP as well as the appearances of any side effects of the drug during the course of the treatment. The results revealed a complete disappearance of hot flushes in 63.6% of menopausal women treated with folic acid 10 mg daily and in 32.1% of menopausal women treated with folic acid 5 mg daily. Folic acid significantly decreased plasma level of MHPG in group I and Ii after treatment, and this effect was more significant in group II than I, i.e. folic acid in a dose of 10 mg daily had a better effect than a smaller dose of 5 mg daily. There was also definite positive correlation between clinical improvements of hot flushes and lowering of plasma levels of MHPG. Folic acid caused significant improvement of total cholesterol in a dose of 10 mg daily and significant improvement in TG with both 5 mg and 10 mg daily with no significant effect on the other cardiovascular risk predictors estimated. Folic acid could be used as a safe nonhonmonal replacement treatment for hot flushes in postmenopausal women

Monoaminergic Activity by Drugs Acting on Adrenergic alpha2-receptors in Rat Hippocampus and Primary Visual Cortex / 대한정신약물학회지

OBJECTIVE: The aim of the this study was to compare the effects of clonidine (a alpha2-adrenoceptor and imidazoline receptor agonist), yohimbine (a selective alpha2-adrenoceptor antagonist) and idazoxan (a alpha2-adrenoceptor and imidazoline receptor antagonist) on extracellular monoamines and their metabolites by using the awakening animal microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in brain regions, which are suggested to have regulatory role in depression. METHODS: We used intracerebral microdialysis in awakening rats by inserting probe through the dorsal hippocampus and occipital cortex especially in primary visual cortex, We studied respective effects of 2.0 mg/kg of clonidine, 5.0 mg/kg of yohimbine, and 5.0 mg/kg of idazoxan on the release of MHPG (a major metabolite of norepinephrine), norepinephrine (NE), DOPAC (a major metabolite of dopamine), and 5-HIAA (a main metabolite of serotonin) by intraperitoneal administration. RESULTS: Clonidine decreased the release of MHPG, NE, DOPAC, and 5-HIAA in both dorsal hippocampus and occipital cortex regions, and there were no significant differences in releasing pattern of all monoamines and their metabolites. Both yohimbine and idazoxan enhanced the release of MHPG, NE, DOPAC, and 5-HIAA in both brain regions, but there were significant differences in releasing pattern of NE and 5-HIAA. Idazoxan induced the delayed and higher efflux of NE and 5-HIAA in the primary visual cortex than yohimbine, but not in the hippocampus. CONCLUSION: This study shows that the selective alpha2-adrenoceptor antagonists increase basal monoamine output and enhance the metabolism of them in the hippocampus and primary visual cortex, and the imidazoline receptor has modulatory role in the regulation of monoamine release in primary visual cortex than hippocampus. It also suggests that high turnover rate of serotonin and norepinephrine in primary visual cortex may contribute to the pathophysiological role in depression.

The Relationship between the Age of Onset and Concentrations of Plasma Homovanillic Acid and 3-Methoxy-4-Hydroxyphenylglycol before and after the Neuroleptic Treatment in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: The authors investigated the possibility of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations in plasma to be biological markers before and after the pharmacological treatment of schizophrenia. METHODS: Twenty-six patients with schizophrenia were enrolled after two week washout of neuroleptics. Baseline sampling was done after washout. Consequent samplings were done at two and four week time-points after neuroleptic treatment. The concentrations of HVA and MHPG were analysed with clinical variables, such as age, age of onset, duration of illness, period of hospitalization, and changes of clinical state. The HVA and MHPG were assayed using high pressure liquid chromatographyelectrochemical detection method. RESULTS: A significant association was observed between the age of onset and plasma HVA concentration in washout state of antipsychotics. The earlier onset group had lower plasma HVA concentration than the late onset group. A significant association was observed between the age of onset and plasma MHPG concentration in washout state of antipsychotics. The earlier onset group had lower plasma MHPG concentration than the late onset group. CONCLUSIONS: The present findings suggest that the activities of dopamine and norepinephrine are different with respect to age of onset in the neuroleptic-naive schizophrenia. Plasma HVA and MHPG concentration can be biological markers for the subgrouping of schizophrenia.

The Understanding of Depression Subtypes

The debate about whether depressive disorders should be divided into categories or arrayed along a continuum has gone for decade, without resolution. In our review, there is more evidence consistent with the spectrum concept than there is with the idea that depressive disorders constitute discrete clusters marked by relatively discontinuous boundaries. First, "depression spectrum", "is there a common genetic factors in bipolar and unipolar affective disorder", "threshold model of depression" and "bipolar spectrum disorder" are reviewed. And, a new subtype of depression is so called SeCA depression that is a stressor-precipitated, cortisol-induced, serotonin-related, anxiety/aggression-driven depression. SeCA depression is discussed. But, there is with the idea that depressive disorders constitute discrete subtypes marked by relatively discontinuous boundaries. This subtypes of depressive disorder were reviewed from a variety of theoretical frames of reference. The following issues are discussed ; Dexamethasone suppression test(DST), TRH stimulation test, MHPG, Temperament Character Inventory(TCI), and heart rate variability(HRV).

Reduction of Central Dopamine Release in Hyperprolactinemia / 대한내분비학회지

Background: Prolactin(PRL) secretion is tonically inhibited by doparnine that originates from the hypothalamic tuberoinfundibular tract and reaches the lactotroph via the hypophyseal portal vessel. Hyperprolactinemia associated with oligomenorrhea-amenorrhea, galactorrhea and/or infertility is mainly due to PRL-secreting pituitary adenoma(PA). The diagnosis of idiopathic hyperprolac- tinemia(IHP) is made, when hyperprolactinemia is sustained and all causes of hyperprolactinemia are excluded without radiological abnormality. It is not known, whether IHP and PA are two distinct entities or two subsequent phases of the same disease. The etiology of both disorders remains unresolved. We investigated that PRL hypersecretion in patients with IHP and PA may be the result of a defect in the central nervous system(CNS)-dopamine release, and that there may be some differences in pathogenesis of both diseases. Methods: We measured 24 hour-urinary dopamine, norepinephrine, epinephrine, and serum and 24 hour-urinary VMA(vanillyl rnandelic acid), HVA(homovanilic acid), DOPAC(3,4-dihydroxy phenylaceticacid), MHPG(3-methoxy 4-hydroxy phenylglycol) in 10 normal controls, 9 patients with IHP, and 17 patients with PA in the early follicular phase. Results: Urinary HVA and DOPAC concentrations, the major metabolites of CNS dopaminergic activity, were signficantly lower in both patients with IHP and PA compared with those in normal controls(p 0.05), whereas they were not different in both disease groups. Dopamine, norepine-phrine, epinephrine, MHPG concentrations were similar to those of the normal controls. Although VMA concentrations of both disease groups were significantly higher than those of normal controls, all of them were within normal range. Conelusion: Although our data are unable to establish the precise biochemical defect responsible for central dopamine deficiency in pathogensis of IHP and PA, we can support the presence of a pathological reduction of brain dopamine activity in IHP and PA.

Marcadores biologicos en Psiquiatria / Biological markers in Psychiatry

In order to determine wheter psycopathology is associated with charactheristic neurochemical changes of psychiatric patients, Noradrenergic; Dopaminergic and Serotoninergic urine compounds were quantified in 50 patients (32 females and 18 males) between 20 and 60 years old. They were classified in four groups, according to DSM-IV criteria; in MAJOR DEPRESSION (MD) 30 cases, OBSESSIVE COMPULSIVE DISEASE (OCD) 9 cases, BIPOLAR DEPRESSION (BD)4 cases and SCHIZOPHRENIA (SZ) 7 cases. The following Amine metabolites were determined in 24 hours urine samples Phenylethilamine (PEA); 3-Metho-4-Hidroxy Phenilglycol (MHPG); 5-Hidroxy-indol acetic acid (5HIAA) Homovanilic acid (HVM); Bufotenine (BU); Ometil Bufotenine (OMBU) and 3-5 Metoxy-NN-Dymethyltryptamine (MNNDMT). The results showed a dicrease of Pea levels in 43 per cent of DM; 33 per cent of OCD; 25 per cent of BP and 42 per cent SZ. MOPEG levels were disminished in 53 per cent of DM; 66 per cent of OCD; 25 per cent of BP and 85 per cent of SZ. There was an increase of HVM levels in 10 per cent of DM; 11 per cent of OCD and 25 per cent of BP. There was a dicrease of 5-HIAA levels in 10 per cent of DM while it was increased in 33 per cent and 14 per cent of SZ, BU, OMBU and NNDMT were positive in 71 per cent of SZ; 46 per cent of DM; 55 per cent of OCD and 50 per cent of BP. Our findings are consistent with the hypothesis that PEA; MHPG; 5-HIAA and HVM compounds could be "State markers"of DM and HVM of BP and SZ patients. There is further evidence to support a close interrelationship between the three systems and the urinary excretion of methylates compounds specially in SZ and in DM, OCD and BP patients.

Incriase of the serotonin metabolite, 5-hydroxyindoleacetic acid, in cerebro-spinal fluid and spinal cord of bovines affected with the paraplegic syndrome

The paraplegic syndrome of bovines is a condition characterized by impairment of locomotion, hypoalgesia and finally death within 72 h. The pathogenesis of the syndrome has not been established. In the present work we determined the levels of monoamines and their metabolites in cerebro-spinal fluid and spinal cord of affected animals in order to investigate the functional state of these neurotransmitters. The content of the main metabolite of serotonin, 5-hydroxyindoleacetic acid, was elevated in the cerebro-spinal fluid and in the gray matter of the spinal cord of paraplegic bovines. Serotonin content in the spinal cord did not differ with respect to control animals, but was decreased in the cerebro-spinal fluid of affected animals. Modifications in the noradrenergic system were also observed, but were less consistent, for which reason further studies are needed. These observations indicate an increase in the turnover rate of serotonin in the paraplegic syndrome. The meaning of the described alterations is unknown at the moment

The relationship between clinical response and urinary MHPG and plasma cortisol level in major depressives treated with tricyclics / 신경정신의학

No abstract available.

Biochemical correlate of depression in children

O grau de depressäo em 88 crianças abandonadas foi analisado por escala de avaliaçäo de depressäo adaptada para crianças na pré-puberdade. Os itens da escala foram agrupados em três dimensöes: sociológico-relacional, psicológica e biológica. Em 46 crianças desta amostra foram dosados o cortisol plasmático e a excreçäo urinária de catecolomina, VMA, HVA e 5-HIAA. Pela análise dos principais componentes, mostraram-se mais importantes, na amostra, as dimensöes sociológica e psicológica, seguidas dos componentes idade e catecolomina. O grupo de crianças do sexo masculino com depressäo apresentava maior nível de excreçäo urinária de catecolomina e menor pico de cortisol plasmático que o grupo sem depressäo. A variável idade, em ambos os sexos, correlacionava-se à variável catecolomina. Alteraçöes bioquímicas estäo presentes em crianças com depressäo, mas é difícil demonstrar correlaçäo de dependência entre elas e aspectos fenomenológicos da depressäo

Neuroquímica das depressoes / Depressions neurochemistry

Por meio de revisao dos dados de literatura os autores discutem os principais aspectos do estudo da neuroquímica das depressoes. Sao revisadas as teorias amnérgicas, sua origem e seu papel atual

Value of DOPEG estimation in CSF in depression.

3,4-Dihydroxyphenyl ethylene glycol (DOPEG), a metabolite of noradrenaline (NA), was estimated in CSF of 30 patients of depression diagnosed by the criteria of American Psychiatric Association in DSM-III; and compared with levels in 10 non-depressed individuals who served as controls. Mean DOPEG levels in CSF in the patient group (801.37 +/- 28.09 micrograms/l) were significantly higher (P less than 0.01) than those in the control group (724.3 +/- 34.62 micrograms/l). Formation of excessive amount of this particular metabolite suggests an excessive intraneuronal deamination of NA, partially accounting for the overall decline in the availability of NA in the noradrenergic neurons in patients of depression.

Neurotransmitters and their Metabolites in the Cerebrospinal Fluid of Normal Adults

The measurement of monoamine neurotransmitters and their metabolites lin the cerebrospinal fluid has important implications for the identification of those disorders assosciated with the central nervous system. The purpose of this study was to measure the concentrations of the biogenic amines and their metabolites using high performance liquid chromatography electrochemical detection (HPLC-ECD) in CSF of normal adults. Sixteen adults who were admitted to Severance Hospital from February to March, 1988 and presented no history of neurological disease with normal CSF findings were included in this study. The results were as follows: 1. Neither dopamine nor norepinephrine were detected in the CSF. 2. Serotonin was detected in 3 cases and 3.4-dihydroxyphenylacetic acid (DOPAC) was measured in 4 cases, but all in small amouints. 3. Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in all 16 cases, but 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) was noted in 12 cases. The mean CSF concentrations of HVA, 5-HIAA, MHPG were 37.01 + 21.14ng/ml (ranging 6.14 - 81.15 ng/ml), respectively. 4. The concentrations of 5-HIAA and MHPG were correlated positively with age, but not the concentration of HVA. 5. Higher concentration of HVA, 5-HIAA and MHPG were found in femalse than males. These results indicate that the metabolites HVA, 5-HIAA and MHPG can be simultaneously measured in the human CSF by using HPLC-ECD, and this information may be valuable for the further study of centarl nervous system diseases.

Revisión y actualización de la sensibilidad diagnóstica del test de la supresión de la dexametasona y de la determinación de feniletilamina y ácido 3-metoxi-4-hidroxi-feniletilglicol urinários en el diagnóstico de la depresión endógena / Review and updating of the diagnostic sensibility of the dexamethazone suppression test and urinary determination of phenylethylamine and 3-methoxy-4-hydroxyphenylglycol in the diagnosis of endogenous depression

Se estudian sesenta pacientes depresivos endógenos (DSM III: 296.2x, 3x y 296.5x) con las siguientes técnicas diagnósticas: DST (Standarization de Carroll), la cuantificación (u) de FEA (Técnica de Spatz) y la cuantificación (u) de MOPEG (Técnica de Bigelow). Se obtienen siete subgrupos, según resulten positivos por lo menos en una de las determinaciones. Se observa una gran sensibilidad al utilizar las tres técnicas, pues sólo un 5% de los pacientes no es detectado. Se discute el camino crítico que conduce a estas conclusiones

En busca de Marcadores biológicos de trastornos afectivos / Searching biological Markess of offective disorders

Se revisan algunos aspectos teóricos y metodológicos en relación a los marcadores biológicos de transtornos afectivos, y se presentan los resultados de la experiencia acumulada en este campo en el Instituto Mexicano de Psiquiatría. Niveles de MHPG urinario > 2800 ug/24 hs, sugieren pocas posibilidades de respuesta al tratamiento farmacológico convencional. El registro polisomnográfico muestra cambios sustanciales en la arquitectura del sueño de los enfermos deprimidos, siendo el acortamiento de la latencia al primer sueño MOR, el que mejor premite distinguirlos de los sujetos sanos. La puebra de supresión con dexametasona, tuvo una confianza diagnóstica del 77%, equiparable a la reportada en otros centros

Utilización del M.H.P.G; H.A y 5-H.I.A.A; como "marcadores biológicos" de la depresión y de la eficacia terapéutica de medicamentos antidepresores / M.H.P.G; H.V.A and 5-H.I.A.A. utilization like biological markers of the depression and therapeutics efficiency of antidepressive agents

Los metabolitos de Catecolaminas y Serotonina (MHPG, HVA y 5-HIAA, respectivamente) fueron determinados utilizando una técnica combinada de Cromatografía de gases y Espectrometría de masas, que permite la dosificación simultánea de estos tres metabolitos, los cuales se determinaron en las orinas de 24 horas de 40 personas normales y 48 pacientes deprimidos (depresión primaria y secundaria). Los resultados obtenidos indican la existencia de una heterogeneidad bioquímica de la depresión, a pesar de la homogeneidad clínica aparente. Las anomalías observadas en este estudio permiten orientar de una cierta manera la selección del fármaco antidepresor en función de sus acciones centrales sobre el metabolismo de la Noradrenalina, la Dopamina y la Serotonina, con el fín de aumentar su eficacia. Estos "índices bioquímicos" podrían constituir en el futuro un medio eficaz de racionalización de la terapéutica psiquiátrica, en especial en el caso de las depresiones