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E Costa

Publications and source records attributed to E Costa.

At least 37 records · Page 2Linked to original sources
PubMed2002

GABAA receptors and benzodiazepines: a role for dendritic resident subunit mRNAs.

This review is designed to describe the evolution of the seminal observation made simultaneously in 1975 by Dr. W. Haefely's laboratory (Hoffman La Roche, Basel, Switzerland) and in the Laboratory of Preclinical Pharmacology (NIH, St. Elizabeths Hospital, Washington DC), that benzodiazepine action was mediated by a modulation of GABA action at GABA(A) receptors. In fact, our suggestion was that the benzodiazepine receptor was "a receptor on a receptor" and that this receptor was GABA(A). Needless to say, this suggestion created opposition, but we did not abandon the original idea, in fact, as shown in this review, there is now universal agreement with our hypothesis on the mode of action of benzodiazepines. Hence, this review deals with the allosteric modulation of GABA(A) receptors by benzodiazepines, the role of GABA(A) receptors and benzodiazepine structure diversities in this modulation, and describes the results of our attempts to establish a benzodiazepine (imidazenil) devoid of tolerance, withdrawal symptoms, and changes in the expression of GABA(A) receptor subunits during tolerance. It also deals with the idea that the synthesis of GABA(A) receptor subunits triggered by tolerance resides in dendrites and spines where mRNAs and the apparatus for this translation is located. New analytic procedures may foster progress in the understanding of tolerance to and withdrawal from benzodiazepines.

Allosteric Regulation↗
PubMed2002

Effect of package and storage conditions on viability and efficacy of the freeze-dried biocontrol agent Pantoea agglomerans strain CPA-2.

AIMS: To reduce concentrations of protective and rehydrating media and to evaluate the effect of storage temperature, packaging and atmosphere conditions on the stability of freeze-dried Pantoea agglomerans cells. Efficacy against Penicillium digitatum of freeze-dried cells in orange fruits was also evaluated. METHODS AND RESULTS: Several concentrations of protective and rehydration media were tested to reduce processing costs. Freeze-dried cells were packed in glass vials or plastic bags under vacuum or nitrogen conditions at 4 and 25 degrees C. After 1 and 3 months, efficacy of freeze-dried P. agglomerans against P. digitatum was tested. CONCLUSIONS: The results indicate that it is possible to reduce the concentration of non-fat skimmed milk as a rehydration medium from 10% to 1%, maintaining viabilities of 100%. Moreover, freeze-dried cells could be stored in glass vials or in high barrier plastic bags at 4 degrees C for 3 months while maintaining high viabilities and efficacy against P. digitatum. SIGNIFICANCE AND IMPACT OF THE STUDY: The major obstacle in the commercialization of biocontrol products is the development of a shelf-stable formulated product that retains biocontrol activity at a level similar to that of fresh cells. This study suggests that it is possible to maintain viability and efficacy of freeze-dried P. agglomerans cells for at least 3 months.

Atmosphere↗
PubMed2002

The role of surgery in stage IV neuroblastoma.

BACKGROUND/PURPOSE: The importance of primary tumor resection in stage IV neuroblastoma is controversial. The authors analyzed prospectively the role of surgery in a multicentric series of stage IV neuroblastoma patients. METHODS: Patients were studied according to the International Neuroblastoma Staging System (INSS) recommendations. Age, sex, location of the tumor, type of metastases, time of resection (initial or delayed), extension of resection, surgical complications, pathology, N-myc and Shimada classification results, relapses, and outcome were studied. After diagnosis, children received induction chemotherapy followed by delayed surgery and autologous stem cell transplantation or maintenance chemotherapy. Resection was classified as complete (C), greater than 90% (P1), greater than 50% (P2), less than 50% (P3), and biopsy (B). RESULTS: Ninety-eight stage IV children were admitted in the study from June 1992 to July 1999. Seventy-six were older than one year, and in 78 the primary tumor was abdominal. Bone was the most common metastatic site followed by bone marrow. Initial biopsy was performed in 74 patients, and resection in 6, with one complication in each group. N-myc was amplified in 20 of 80 tumors, and Shimada was unfavorable in 45 of 67. Delayed surgery was performed in 70 cases, achieving gross total resection in 55 (79%); there were minor complications in 10%. Mean survival rate time was 50 months. Event-free survival rate (EFS) at 5 years for the entire series is 0.32, but 0.0 for children having biopsy only, 0.25 for less than 50% resection, 0.31 for 50% to 90% resection, 0.44 for greater than 90% resection, and 0.33 for complete resection. Differences were statistically significant only when compared with the biopsied group. EFS rate for infants was 0.56, but, again, there was no difference in relation to the type of resection. There were 46 relapses, 12 of them local, 7 of 20 N-myc-amplified tumors, and 4 of 60 not amplified (P <.005). CONCLUSIONS: Biopsies of stage IV neuroblastoma allow safe assessment of N-myc and other biological factors on tumor tissue. Delayed surgery after chemotherapy is performed with a low rate of complications, achieving a good local control of disease. N-myc-amplified tumors have higher local relapse rates than nonamplified and therefore would need more intensive local treatment. The final outcome in these patients is determined more by metastatic relapses than by the degree of resection.

Abdominal Neoplasms↗
PubMed2002

Study of the influence of the pH media dissolution, degree of polymerization, and degree of swelling of the polymers on the mechanism of release of diltiazem from matrices based on mixtures of chitosan/alginate.

The dissolution profiles of formulations based on mixtures of chitosan/alginate depend on the pH. It is possible to distinguish two processes: (a) a fast kinetic drug release up to 180 min, where the pH value changes from 1.17 to 2.21 and the drug released is controlled by the degree of polymerization and the quantity of chitosan in the formulation; (b) a low kinetic drug release between 210 and 480 min, where the pH value changes from 5.52 to 8.72 and the drug release from the matrix is controlled by the interpolymeric complex. In all formulations the order of release, according to Peppas's model in the range of fast kinetic drug release, was between 0.5 and 1.0. The mechanism of release was non-fickian diffusion, which corresponds to a coupling mechanism of diffusion and relaxation of the polymer.

Alginates↗
PubMed2002

REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.

The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.

Animals↗
PubMed2002

Water activity, temperature, and pH effects on growth of the biocontrol agent Pantoea agglomerans CPA-2.

The growth response of the biocontrol agent Pantoea agglomerans to changes in water activity (a(w)), temperature, and pH was determined in vitro in nutrient yeast extract-sucrose medium. The minimum temperature at which P. agglomerans was able to grow was 267-272 kelvins (-6 to -1 degrees C), and growth of P. agglomerans did not change at varying pH levels (4.5-8.6). The minimum a(w) for growth was 0.96 in media modified with glycerol and 0.95 in media modified with NaCl or glucose. Solute used to reduce water activity had a great influence on bacterial growth, especially at unfavourable conditions (e.g., low pH or temperature). NaCl stimulated bacterial growth under optimum temperatures but inhibited it under unfavourable pH conditions (4.5 or 8.6). In contrast, the presence of glucose in the medium allowed P. agglomerans to grow over a broad range of temperature (3-42 degrees C) or pH (5-8.6) regimes. This study has defined the range of environmental conditions (a(w), pH, and temperature) over which the bacteria may be developed for biological control of postharvest diseases.

Biomass↗
PubMed2002

Survival of Pantoea agglomerans strain CPA-2 in a spray-drying process.

Spray drying could be a suitable method for preserving microorganisms, as it allows large quantities of cultures to be dried at low cost. The aims of this paper were to evaluate the effects of spray-drying conditions on survival of the biocontrol agent Pantoea agglomerans CPA-2, which has shown antifungal activity against Penicillium expansum and Penicillium digitatum on citrus fruits. Various compounds cited in the bibliography as carriers were tested in our spray drying, and some salts (MgSO4, K2SO4. and Na2CO3) and dairy products (lactoserum or nonfat skimmed milk [NFSM]) showed the best results in terms of recovered powder. Outlet temperature had more influence on the death of bacteria than inlet temperature. P. agglomerans was heat sensitive, and the activation energy was around 6 kcal/mol K when MgSO4 (10%) or NFSM (10%) were used as carriers and only 3 kcal/mol K when the combination of MgSO4 (10%) and NFSM (10%) was used. The highest powder recovery was obtained when NFSM was used as the rehydration medium. Although the percentage of powder recovery was not high (around 50%) and viability was low, the results suggest that with bigger spray dryers, we could expect a lower outlet temperature and probably an increased viability. Further research into spray-dryer design is needed in order to demonstrate this.

Biotechnology↗
PubMed2002

[Influence of Gilbert's syndrome on serum bilirubin levels and gallstone formation in children with chronic hemolytic disease].

To determine whether Gilbert's syndrome increases the risk of gallstone formation in children with chronic hemolytic disease, we studied 44 children with this diagnosis. Gallstones were detected by abdominal ultrasonography. This took place annually in scheduled examinations or in the context of acute abdominal pain. In all patients, the mean values of hemoglobin, reticulocyte and serum bilirubin in the chronic phase were recorded. In addition, TA insertion in the A(TA)nTATAA motif within the promoter region of the enzyme uridine-diphosphate-glucuronyl transferase (UGT1A1) was screened, since this is typically associated with GS.We found 10 (22.7 %) homozygotes for the mutated allele TA*7/TA*7, 12 (27.3 %) TA*6/TA*6 heterozygotes and 22 (50 %) homozygotes for the wild-type allele TA*6/TA*6. No statistically significant differences were found in the values of hemoglobin (Kruskal-Wallis test 2.496; p > 0.05) or in reticulocyte count (Kruskal-Wallis test 1.696; p > 0,05) between the three groups of patients, suggesting a similar degree of hemolysis. Patients with the UGT1A1 TA*7/TA*7 genotype showed higher mean serum bilirubin levels than did patients who were homozygous for the wild-type allele (Mann-Whitney test 35.5; p < 0.05). None of the patients with the TA*6/TA*6 genotype developed gallstones, whereas this complication was found in 2 of 12 (16.6 %) heterozygotes and 6 of 10 (60 %) homozygotes for the allele with TA insertion. In this latter group, 4 patients presented acute pancreatitis as a consequence of gallstone formation.The association between increased bilirubin load due to chronic hemolytic disease and diminished hepatic conjugation leads to raised serum bilirubin levels and consequently to an increased risk of gallstone formation. Therefore, we recommend screening for Gilbert's syndrome in children in the initial phases of chronic hemolytic diseases.

Bilirubin↗
PubMed2002

Study of the prolonged release of theopylline from polymeric matrices based on grafted chitosan with acrylamide.

The aim of this work was to study the performance of chitosan (CB) grafted with acrylamide (CB-g-A) as prolonged drug release matrix as compared with unmodified chitosan. A non-pH dependent swelling behaviour for the matrix tablets based on grafted chitosan was observed. The overlaping between degree of swelling measured by weighing (DSw) and measured by increase of diameter (DSd) up to 240 minutes showed that the swelling process could be isotropic. The non-pH dependent swelling behaviour of these matrices could be explained by the partial substitution of amine groups of the chitosan chain by acrylamide. The grafting reaction provides an ionizable amine group by a neutral amide group which make the matrix non pH-dependent. On the contrary, the matrix tablet based on chitosan showed a pH dependent swelling behaviour where the swelling process could be anisotropic. The higher degree of erosion and swelling of the formulation based on CB-g-A600 (%G = 600) compared with the formulation based on chitosan and CB-g-A418 (%G = 418) could explain the higher fraction of theopylline released. For all formulations studied in this work, the amount of theopylline released from the matrix tablets was found to be controlled by a combination of the diffusion process and relaxation of the polymeric structure. These results match with the controlled swelling behaviour and low degree of erosion observed for these systems.

Acrylamides↗
PubMed2001

An efficient photoelectric X-ray polarimeter for the study of black holes and neutron stars.

The study of astronomical objects using electromagnetic radiation involves four basic observational approaches: imaging, spectroscopy, photometry (accurate counting of the photons received) and polarimetry (measurement of the polarizations of the observed photons). In contrast to observations at other wavelengths, a lack of sensitivity has prevented X-ray astronomy from making use of polarimetry. Yet such a technique could provide a direct picture of the state of matter in extreme magnetic and gravitational fields, and has the potential to resolve the internal structures of compact sources that would otherwise remain inaccessible, even to X-ray interferometry. In binary pulsars, for example, we could directly 'see' the rotation of the magnetic field and determine if the emission is in the form of a 'fan' or a 'pencil' beam. Also, observation of the characteristic twisting of the polarization angle in other compact sources would reveal the presence of a black hole. Here we report the development of an instrument that makes X-ray polarimetry possible. The factor of 100 improvement in sensitivity that we have achieved will allow direct exploration of the most dramatic objects of the X-ray sky.

Journal Article↗
PubMed2001

Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse.

Heterozygous reeler mice (HRM) haploinsufficient for reelin express approximately 50% of the brain reelin content of wild-type mice, but are phenotypically different from both wild-type mice and homozygous reeler mice. They exhibit, (i) a down-regulation of glutamic acid decarboxylase 67 (GAD(67))-positive neurons in some but not every cortical layer of frontoparietal cortex (FPC), (ii) an increase of neuronal packing density and a decrease of cortical thickness because of neuropil hypoplasia, (iii) a decrease of dendritic spine expression density on basal and apical dendritic branches of motor FPC layer III pyramidal neurons, and (iv) a similar decrease in dendritic spines expressed on the basal dendrite branches of CA1 pyramidal neurons of the hippocampus. To establish whether the defect of GAD(67) down-regulation observed in HRM is responsible for neuropil hypoplasia and decreased dendritic spine density, we studied heterozygous GAD(67) knockout mice (HG(67)M). These mice exhibited a down-regulation of GAD(67) mRNA expression in FPC (about 50%), but they expressed normal amounts of reelin and had no neuropil hypoplasia or down-regulation of dendritic spine expression. These findings, coupled with electron-microscopic observations that reelin colocalizes with integrin receptors on dendritic spines, suggest that reelin may be a factor in the dynamic expression of cortical dendritic spines perhaps by promoting integrin receptor clustering. These findings are interesting because the brain neurochemical and neuroanatomical phenotypic traits exhibited by the HRM are in several ways similar to those found in postmortem brains of psychotic patients.

Animals↗
PubMed2001

Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines.

Protracted administration of diazepam elicits tolerance, whereas discontinuation of treatment results in signs of dependence. Tolerance to the anticonvulsant action of diazepam is present in an early phase (6, 24, and 36 h) but disappears in a late phase (72-96 h) of withdrawal. In contrast, signs of dependence such as decrease in open-arm entries on an elevated plus-maze and increased susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not 12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal, tolerance is associated with changes in the expression of GABA(A) (gamma-aminobutyric acid type A) receptor subunits (decrease in gamma(2) and alpha(1); increase in alpha(5)) and with an increase of mRNA expression of the most abundant form of glutamic acid decarboxylase (GAD), GAD(67). In contrast, dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit mRNA and cognate protein, which are normal during the early phase of diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in association with the appearance of signs of dependence 96 h after diazepam withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold-immunolabeling technique reveal that the increase of GluR1 subunit protein is localized to layer V pyramidal neurons and their apical dendrites in the cortex, and to pyramidal neurons and in their dendritic fields in hippocampus. The results suggest an involvement of GABA-mediated processes in the development and maintenance of tolerance to diazepam, whereas excitatory amino acid-related processes (presumably via AMPA receptors) may be involved in the expression of signs of dependence after withdrawal.

Animals↗
PubMed2001

Engineering of efficient panchromatic sensitizers for nanocrystalline TiO(2)-based solar cells.

A new series of panchromatic ruthenium(II) sensitizers derived from carboxylated terpyridyl complexes of tris-thiocyanato Ru(II) have been developed. Black dye containing different degrees of protonation [(C(2)H(5))(3)NH][Ru(H(3)tcterpy)(NCS)(3)] 1, [(C(4)H(9))(4)N](2)[Ru(H(2)tcterpy)(NCS)(3)] 2, [(C(4)H(9))(4)N](3)[Ru(Htcterpy)(NCS)(3)] 3, and [(C(4)H(9))(4)N](4)[Ru(tcterpy)(NCS)(3)] 4 (tcterpy = 4,4',4' '-tricarboxy-2,2':6',2' '-terpyridine) have been synthesized and fully characterized by UV-vis, emission, IR, Raman, NMR, cyclic voltammetry, and X-ray diffraction studies. The crystal structure of complex 2 confirms the presence of a Ru(II)N6 central core derived from the terpyridine ligand and three N-bonded thiocyanates. Intermolecular H-bonding between carboxylates on neighboring terpyridines gives rise to 2-D H-bonded arrays. The absorption and emission maxima of the black dye show a bathochromic shift with decreasing pH and exhibit pH-dependent excited-state lifetimes. The red-shift of the emission maxima is due to better pi-acceptor properties of the acid form that lowers the energy of the CT excited state. The low-energy metal-to-ligand charge-transfer absorption band showed marked solvatochromism due to the presence of thiocyanate ligands. The Ru(II)/(III) oxidation potential of the black dye and the ligand-based reduction potential shifted cathodically with decreasing number of protons and showed more reversible character. The adsorption of complex 3 from methoxyacetonitrile solution onto transparent TiO(2) films was interpreted by a Langmuir isotherm yielding an adsorption equilibrium constant, K(ads), of (1.0 +/- 0.3) x 10(5) M(-1). The amount of dye adsorbed at monolayer saturation was (n(alpha) = 6.9 +/- 0.3) x 10(-)(8) mol/mg of TiO(2), which is around 30% less than that of the cis-di(thiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II) complex. The black dye, when anchored to nanocrystalline TiO(2) films achieves very efficient sensitization over the whole visible range extending into the near-IR region up to 920 nm, yielding over 80% incident photon-to-current efficiencies (IPCE). Solar cells containing the black dye were subjected to analysis by a photovoltaic calibration laboratory (NREL, U.S.A.) to determine their solar-to-electric conversion efficiency under standard AM 1.5 sunlight. A short circuit photocurrent density obtained was 20.5 mA/cm(2), and the open circuit voltage was 0.72 V corresponding to an overall conversion efficiency of 10.4%.

Journal Article↗
PubMed2001

Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation.

Allopregnanolone (ALLO), is a brain endogenous neurosteroid that binds with high affinity to gamma-aminobutyric acid type A (GABA(A)) receptors and positively modulates the action of GABA at these receptors. Unlike ALLO, 5alpha-dihydroprogesterone (5alpha-DHP) binds with high affinity to intracellular progesterone receptors that regulate DNA transcription. To investigate the physiological roles of ALLO and 5alpha-DHP synthesized in brain, we have adopted a mouse model involving protracted social isolation. In the frontal cortex of mice, socially isolated for 6 weeks, both neurosteroids were decreased by approximately 50%. After administration of (17beta)-17-(bis-1-methyl amino carbonyl) androstane-3,5-diene-3-carboxylic acid (SKF105,111), an inhibitor of the enzyme (5alpha-reductase Type I and II) that converts progesterone into 5alpha-DHP, the ALLO and 5alpha-DHP content of frontal cortex of both group-housed and socially isolated mice decreased exponentially to 10%-20% of control values in about 30 min. The fractional rate constants (k h(-1)) of ALLO and 5alpha-DHP decline multiplied by the ALLO and 5alpha-DHP concentrations at any given steady-state estimate the rate of synthesis required to maintain that steady state. After 6 weeks of social isolation, ALLO and 5alpha-DHP biosynthesis rates were decreased to 30% of the values calculated in group-housed mice. Moreover, in socially isolated mice, the expression of 5alpha-reductase Type I mRNA and protein was approximately 50% lower than in group-housed mice whereas 3alpha-hydroxysteroid oxidoreductase mRNA expression was equal in the two groups. Protracted social isolation in mice may provide a model to investigate whether 5alpha-DHP by a genomic action, and ALLO by a nongenomic mechanism down-regulate the action of drugs acting as agonists, partial agonists, or positive allosteric modulators of the benzodiazepine recognition sites expressed by GABA(A) receptors.

Animals↗
PubMed2001

Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability.

In this review, we will first present a brief overview of the current understanding of: (a) the biology of reelin; (b) the putative reelin signaling pathways via integrin receptor stimulation; (c) the cytosolic adapter protein DAB1, which appears to be operative in the transduction of reelin's pleiotropic actions in embryonic, adolescent, and adult brain; (d) the regulation of GABAergic function, including some aspects of GABAergic system development; and (e) dendritic spine function and its role in the regulation of synaptic plasticity. We argue that a downregulation of reelin expression occurring in prefrontal cortex and in every brain structure of schizophrenia patients so far studied may be associated with a decrease in dendritic spine expression that in turn may provide an important reduction of cortical function as documented by the downregulation of glutamic acid decarboxylase67 (GAD67) expression, which might be secondary to a reduction of GABAergic axon terminals. This hypothesis is supported by a genetic mouse model of reelin haploinsufficiency that replicates the above-described dendritic and presynaptic GABAergic defects documented in schizophrenia brains.

Adolescent↗
PubMed2001

Production of the biocontrol agent Pantoea agglomerans strain CPA-2 using commercial products and by-products.

The aim of this paper was to find the nitrogen and carbon sources that provide maximum biomass production of strain CPA-2 of the biocontrol agent Pantoea agglomerans and minimum cost of media, whilst maintaining biocontrol efficacy. To reduce the cost of media, commercial products and by-products were tested. P. agglomerans can be produced using a combination of nitrogen sources such as yeast extract (5 g l(-1)) and dry beer yeast (10 g l(-1)) with inexpensive carbohydrates such as sucrose (10 g l(-1)) and molasses (20 g l(-1)), respectively, maintaining the efficacy of the biocontrol agent against Penicillium digitatum and P. italicum on oranges. The results obtained in this study could be used to provide a reliable basis for a scale-up of this fermentation process to an industrial level.

Biomass↗
PubMed2001

The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders.

Allopregnanolone (3alpha,5alpha-TH PROG) and 5alpha-dihydroprogesterone (5alpha-DH PROG), the two most important neuroactive steroids synthesized in the brain, potently modulate neuronal activity by allosterically regulating GABA action at GABA(A) receptors or by changing specific GABA(A) receptor subunit gene expression, respectively. We recently reported [Proc. Natl. Acad. Sci. USA 95 (1998) 3239] that in patients with severe depression there is a decrease in the CSF levels of 3alpha,5alpha-TH PROG, which is normalized by treatment with drugs (i.e. fluoxetine) that improve psychopathology. The mechanism by which fluoxetine and other selective serotonin reuptake inhibitors normalize 3alpha,5alpha-TH PROG CSF levels appears to involve a direct stimulation of 3alpha-hydroxysteroidoxidoreductase (3alpha-HSD), an enzyme that catalyses the reduction of 5alpha-DH PROG into 3alpha,5alpha-TH PROG. Here, we propose the use of socially-isolated mice that have a downregulation of 3alpha,5alpha-TH PROG and of 5alpha-DH PROG expression to establish a model to study the behavioral consequences of this deficiency. After 4-6 weeks of isolation, these mice exhibit increased anxiety and aggressive behavior and also a decreased response to the administration of GABA-mimetic drugs. In these mice, the decrease in 3alpha,5alpha-TH PROG is selectively normalized by the use of fluoxetine in doses that reduce behavioral abnormalities. In addition, the expression of 5alpha-reductase Type I mRNA and protein was lower in socially-isolated mice than that in group-housed mice whereas 3alpha-HSD mRNA expression remained unchanged. The results of these studies may enable us to design drugs that specifically affect neurosteroidogenic enzymatic activities and may provide an efficacious treatment for the psychopathologies associated with psychiatric disorders.

20-alpha-Dihydroprogesterone↗