This proposal predicts that depletion of CoREST should improve th

This proposal predicts that depletion of CoREST should improve the plaque-forming efficiency and replication of ICP0 null mutant virus. To test this hypothesis, human HepaRG cells that were highly depleted of CoREST were isolated using RNA interference technology.

Depletion of CoREST had no effect on the replication of ICP0 null mutant HSV-1, demonstrating that CoREST does not play an influential role in regulating HSV-1 infection in this cell type.”
“Here learn more we describe a novel vaccine vector for expressing human immunodeficiency virus (HIV) antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting. These recombinant YF17D-induced SIVspecific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.”
“Major life events involving social rejection are strongly associated with onset of depression. To account for this relation, we propose a psychobiological model in which rejection-related stressors elicit a distinct and integrated set of

cognitive, emotional, and biological changes that may evoke depression. In this model, social rejection events activate brain regions involved

in processing negative Milciclib datasheet affect and rejection-related distress (e.g., anterior insula, dorsal anterior cingulate cortex). They also elicit negative self-referential cognitions (e.g., “”I’m undesirable,”" “”Other people don’t like me”") and related self-conscious emotions (e.g., shame, humiliation). Downstream biological consequences include upregulation of the hypothalamic-pituitary-adrenal axis, sympathetic-adrenal-medullary axis, and inflammatory response. Pro-inflammatory cytokines play an important role in this process because they induce a constellation of depressotypic behaviors called sickness others behaviors. Although these changes can be short-lived, sustained inflammation may occur via glucocorticoid resistance, catecholamines, sympathetic innervation of immune organs, and immune cell aging. This response also may be moderated by several factors, including prior life stress, prior depression, and genes implicated in stress reactivity. (C) 2010 Elsevier Ltd. All rights reserved.”
“The crystal structure of the dimerization domain of rabies virus phosphoprotein was determined. The monomer consists of two alpha-helices that make a helical hairpin held together mainly by hydrophobic interactions. The monomer has a hydrophilic and a hydrophobic face, and in the dimer two monomers pack together through their hydrophobic surfaces.

In LPS treated co-cultured astrocytes the mu-opioid receptor anta

In LPS treated co-cultured astrocytes the mu-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca2+ transients. These results suggest that opioids, especially mu-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with mu-opioid receptors, also may act through some binding

site on astrocytes, other than the classical opioid receptor. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: We investigated the effect of Glubran (R) 2 cyanoacrylic glue on rat cavernous tissue after forming penile fractures experimentally as well as the histopathological effect. We also investigated its clinical use.

Materials and Methods: Experimental penile fracture was formed by incising PSI-7977 datasheet from the proximal selleck chemical dorsal side of the penis in 32 Wistar Albino rats. The rats were randomly assigned to 4 main groups of 8 each. In the control

group the incision was not repaired and it was left to secondary healing. In the glue group cyanoacrylic glue was only applied to the incision region. In the primary repair group the incision was primarily repaired and in the final group cyanoacrylic glue was applied to the incision region following primary repair. Three weeks later penectomy materials were examined histopathologically.

Results: When the control group was compared with the other groups, the differences in cavernous tissue healing with fibrosis and hyperemia-bleeding were statistically significant (p = 0.043 and 0.003, respectively). In the glue group fibrosis was observed in 2 rats. This group was the best according to cavernous healing. Although there was no significant difference between the control group and

the other groups according to inflammation (p = 0.057), the glue group was better than the primary repair group (p = 0.026). No significant inflammation or hyperemia-bleeding was observed in the glue group. When the experimental groups were evaluated CHIR99021 for histopathological parameters, it was observed that the best results were obtained in the glue group.

Conclusions: Cyanoacrylic glue can be used in cavernous surgery due to its hemostatic, adhesive and anti-inflammatory properties.”
“By using the patch-clamp technique in the cell-attached configuration, we have investigated the single-channel properties of an inward rectifier potassium channel (Kir) expressed by pigeon vestibular type II hair cells in situ. In high-K+ external solution with 2 mM Mg2+, Kir inward current showed openings to at least four amplitude levels. The two most frequent open states (L2 and L3) had a mean slope conductance of 13 and 28 pS, respectively. L1 (7 pS) and L4 (36 pS) together accounted for less than 6% of the conductive state. Closed time distributions were fitted well using four exponential functions, of which the slowest time constant (tau(C4)) was clearly voltage-dependent.

This component has the same antecedent conditions as P3a, but is

This component has the same antecedent conditions as P3a, but is earlier and more centrally Quizartinib purchase distributed. Its spatiotemporal characteristics suggest that it may be the eP3a component recently described in passive oddball tasks.”
“The central nervous system has been considered off-limits to antibody therapeutics. However, recent advances in preclinical

and clinical drug development suggest that antibodies can cross the blood-brain barrier in limited quantities and act centrally to mediate their effects. In particular, immunotherapy for Alzheimer’s disease has shown that targeting beta amyloid with antibodies can reduce pathology in both mouse models and the human brain, with strong evidence supporting a central mechanism of action. These findings have fueled GSK2118436 molecular weight substantial efforts to raise antibodies against other central nervous system targets, particularly neurodegenerative targets, such as tau, beta-secretase, and alpha-synuclein. Nevertheless, it is also apparent that antibody penetration across the blood-brain barrier

is limited, with an estimated 0.1-0.2 % of circulating antibodies found in brain at steady-state concentrations. Thus, technologies designed to improve antibody uptake in brain are receiving increased attention and are likely going to represent the future of antibody therapy for neurologic diseases, if proven safe and effective. Herein we review briefly the progress and limitations of traditional antibody drug development for neurodegenerative diseases, with a focus on passive immunotherapy. We also take a more in-depth look at new technologies for improved delivery of antibodies to the brain.”
“Hepatitis C virus (HCV) has been shown to induce autophagy and the unfolded protein response (UPR), but the mechanistic link between the induction of these two cellular processes remains unclear. We demonstrate here that HCV infection induces autophagy, as judged by accumulation of lipidated selleck kinase inhibitor LC3-II, and that this induction occurs rapidly after infection, preceding the stimulation of the UPR, which occurs only at later stages, after the viral envelope glycoproteins have been expressed to high levels. Furthermore,

both genotype 1b and 2a subgenomic replicons expressing nonstructural (NS3-5B) proteins and JFH-1 virus lacking the envelope glycoproteins potently induced autophagy in the absence of detectable UPR. This ability was also shared by a subgenomic replicon derived from the related GB virus B (GBV-B). We also show that small interfering RNA (siRNA)-mediated silencing of the key UPR inducer, Ire1, has no effect on HCV genome replication or the induction of autophagy, further demonstrating that the UPR is not required for these processes. Lastly, we demonstrate that the HCV replicase does not colocalize with autophagosomes, suggesting that the induction of autophagy is not required to generate the membrane platform for HCV RNA replication.

At the 6-h and 24-h time points, there was evidence of a minor am

At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid.

Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [(18)F]6FDG

are negligible. (C) 2011 Elsevier Inc. All rights reserved.”
“Introduction: The present investigation focuses on the chemical and biological fate of Zr-89 in mice. Electrophoreses of Zr-89 solvated or chelated in different conditions are here presented. The biological fate of mice injected with [Zr-89]Zr-oxalate, [Zr-89]Zr-chloride, [Zr-89]Zr-phosphate, [Zr-89]Zr-desferrioxamine and [Zr-89]Zr-citrate is studied with the biodistribution, the clearances and positron emission tomography images. A special focus Selisistat clinical trial is also given regarding the quality of Zr-89 bone accumulation.

Methods: Electrophoreses were carried GKT137831 price out on chromatography paper and read by gamma counting. Then, the solutions

were intravenously injected in mice, imaged at different time points and sacrificed. The bones, the epiphysis and the marrow substance were separated and evaluated with gamma counts.

Results: The clearances of [Zr-89]Zr-chloride and [Zr-89]Zr-oxalate reached 20% of injected dose (ID) after 6 days whereas [Zr-89]Zr-phosphate was only 5% of ID. [Zr-89-]Zr-citrate and [Zr-89]Zr-DFO were noticeably excreted after the first day postinjection (p.i.). [Zr-89]Zr-chloride and [Zr-89]Zr-oxalate resulted in a respective bone uptake of similar to 15% ID/g and similar to 20% ID/g at 8 h p.i. with minor losses after 6 days. [Zr-89]Zr-citrate bone uptake was also observed, but [Zr-89]Zr-phosphate was absorbed in high amounts in the liver and the spleen. The marrow cells were insignificantly radioactive in comparison to the calcified tissues.

Conclusion: Despite the complexity of Zr coordination, the electrophoretic

analyses provided detailed evidences of Zr charges either as salts or as complexes. This study also shows that weakly chelated, Zr-89 is a bone seeker and has a strong affinity for phosphate. (C) 2011 Elsevier Inc. All rights reserved.”
“Human adenoviruses (HAdV) AZD9291 manufacturer and JC polyomaviruses (JCPyV) have been proposed as markers of fecal/urine contamination of human origin. An indirect immunofluorescence assay has been developed to quantify infectious human adenoviruses types 2 and 41 and JC polyomaviruses strain Mad-4 in water samples. The immunofluorescence assay was compared with other quantitative techniques used commonly such as plaque assay, tissue culture infectious dose-50 and quantitative PCR (qPCR). The immunofluorescence assays showed to be specific for the detection of infectious viruses, obtaining negative results when UV or heat-inactivated viruses were analyzed.

Neural stem cells (NSCs) can differentiate

into neurons,

Neural stem cells (NSCs) can differentiate

into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the therapeutic effects of transplanting NSCs into rats which have the animal model of Alzheimer’s disease (AD). NSCs from the hippocampus and NSCs-derived glial cells labeled with 5′-Bromo-2′-deoxyuridine (BrdU) were transplanted into two groups of transected rat basal forebrain. Nestin staining, glial fibrillary acidic protein (GFAP) staining and double-labeling immunofluorescence were used to detect the engrafted cells in the basal forebrain. Immunohistochemical detection of p75(NGFR) showed that the number of cholinergic neurons of the NSCs-transplanted group was significant higher than that of the glia-transplanted group in medial septum (MS) and vertical PF-02341066 chemical structure diagonal

branch (VDB) (P < 0.05). Learning and memory abilities were also measured by Y-maze test. The results indicate that transplanted NSCs can differentiate into cholinergic neurons, which may play an important role in the therapeutic effects of transplanted NSCs. Crown Copyright (C) 2008 Published by Elsevier Ireland Ltd. All rights reserved.”
“Combined open and endovascular hybrid procedures can be used to treat complex aortic pathology. This article reports a five-stage hybrid repair for a complex thoracoabdominal aneurysm with dissection in a 57-year-old man. To our knowledge, this is selleck kinase inhibitor Eltanexor supplier the first reported case of replacement and exclusion of the entire native human

aorta from the root to the iliac bifurcations using a combined open and endovascular approach without neurologic complication. Bilateral hypogastric and femoral circulation was preserved. Aggressive spinal protective measures, including spinal drainage, motor-evoked potentials, and prevention of intraoperative and perioperative hypotension, were used during this staged approach. (J Vasc Surg 2008;48:1593-6.)”
“Bradykinin has been shown to increase the permeability of blood-tumor barrier (BTB) selectively. This study was performed to determine whether tumor necrosis factor-alpha (TNF-alpha) was involved in the regulation of this biological process. We found that the levels of TNF-alpha mRNA and heat shock factor-1 (HSF1) protein in C6 cells were markedly up-regulated by bradykinin via real-time RT-PCR and Western blot methods. And the most obvious increase of HSF1 protein and TNF-alpha mRNA in C6 cells were observed at 5 min and 10 min of bradykinin perfusion, respectively. In addition, the radioactivity of TNF-alpha in C6 cells’ culture fluid also mostly increased at 15 min of bradykinin perfusion. And the Evans blue content of brain tumor tissues in rats and the concentration of TNF-alpha reached the maximum at 15 min of bradykinin perfusion.

However, the mechanisms of HIV-1 infection-mediated T cell dysfun

However, the mechanisms of HIV-1 infection-mediated T cell dysfunction are not completely understood. Here, we provide evidence that expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) suppressed T cell function in HIV-1-infected individuals. We observed a dramatic elevation of M-MDSCs (HLA-DR-/low CD11b(+) CD33(+/high) CD14(+) CD15(-) cells) in the peripheral blood of HIV-1-seropositive subjects (n = 61) compared with healthy controls (n = 51), despite efficacious antiretroviral therapy for

nearly 2 years. The elevated M-MDSC frequency in HIV-1(+) subjects correlated with prognostic HIV-1 disease markers, including the HIV-1 load (r = 0.5957; P < 0.0001), CD4(+) T cell loss (r = -0.5312; P < 0.0001), and activated T cells (r = 0.4421; EPZ004777 supplier P = 0.0004). Functional studies showed that M-MDSCs from HIV-1(+) subjects suppressed T cell responses in both HIV-1-specific and antigen-nonspecific manners; this effect was dependent on the induction of arginase 1 and required direct

cell-cell contact. Further investigations revealed that direct HIV-1 infection or culture with HIV-1-derived Tat protein significantly selleck chemicals llc enhanced human MDSC generation in vitro, and MDSCs from healthy donors could be directly infected by HIV-1 to facilitate HIV-1 replication and transmission, indicating that a positive-feedback loop between HIV-1 infection and MDSC expansion existed. In summary, our studies revealed a novel mechanism of T cell dysfunction in HIV-1-infected individuals and suggested that targeting MDSCs may be a promising strategy for HIV-1 immunotherapy.”
“Reduced motor activity has been reported in schizophrenia and was associated with subtype, psychopathology and medication. Still, little is known about the neurobiology of motor retardation. To identify neural correlates of motor activity, resting state cerebral blood flow (CBF) was correlated with objective motor activity of the same day. Participants

comprised 11 schizophrenia patients and 14 controls who underwent magnetic resonance imaging with arterial spin labeling and wrist actigraphy. Patients had reduced activity levels and reduced perfusion of the left parahippocampal gyrus, left middle temporal gyms, right selleck products thalamus, and right prefrontal cortex. In controls, but not in schizophrenia, CBF was correlated with activity in the right thalamic ventral anterior (VA) nucleus, a key module within basal ganglia-cortical motor circuits. In contrast, only in schizophrenia patients positive correlations of CBF and motor activity were found in bilateral prefrontal areas and in the right rostral cingulate motor area (rCMA). Grey matter volume correlated with motor activity only in the left posterior cingulate cortex of the patients. The findings suggest that basal ganglia motor control is impaired in schizophrenia.

Although this association was more apparent in older persons, it

Although this association was more apparent in older persons, it did not appear to be influenced by cigarette smoking.”
“The attachment of Y-27632 clinical trial a sugar moiety to the 3-hydroxy group of a sterol drastically increases the size of the hydrophilic part of the lipid. It is obvious that the glycosylation of a considerable fraction of membrane-bound free sterols alters the biophysical properties of the membrane. However, the consequences of such changes in the proportions of free sterols and steryl glycosides on the biological functions of a membrane are still unclear. This is the main hurdle

in understanding the biological functions of steryl glycosides on a molecular level. The recent cloning of sterol glycosyltransferase genes from plants, fungi and bacteria has enabled genetic approaches to analyze steryl glycoside functions. Down regulation of phytosteryl beta-glycoside

biosynthesis in Arabidopsis thaliana causes several dysfunctions in seed development. Ergosteryl beta-glycoside depleted mutants of the yeast Pichia pastoris lose their ability to degrade their peroxisomes by an autophagic mechanism called micropexophagy. selleck inhibitor In the plant-pathogenic fungus Colletotrichum orbiculare the same defect impairs invasion of the cucumber host plants. Helicobacter pylori, a bacterium colonizing the human stomach, is unable to modulate the host’s immune response when the cholesteryl alpha-glycoside biosynthesis of the bacterium is mutated. These mutants with manipulated steryl glycoside metabolism will inspire

further studies with cell biological, biophysical and other methods that will provide us with a mechanistic understanding of steryl glycoside functions. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objectives: Transection of the secondary chordae on the anterior leaflet of the mitral valve to relieve leaflet tethering and reduce regurgitation is an experimentally proven procedure to correct functional mitral regurgitation. In the present study, we sought to investigate whether transecting the secondary chordae would have an effect on the marginal chordal Sitaxentan force on the same leaflet.

Methods: Adult porcine mitral valves (n = 8) were studied in a pulsatile heart simulator, in which the papillary muscle positions can be precisely positioned. Miniature transducers were inserted into the anterior marginal chordae to measure the chordal forces. Each valve was studied under baseline conditions, 3 different tethering conditions (apical, apical-lateral, and apical-lateral-posterior), and after chordal cutting in the 3 tethering conditions. The temporal changes and peak and average marginal chordal forces under each condition are reported.

Results: Apical tethering increased the marginal chordal force by an average of 96% but remained unchanged after chordal cutting.

elegans and mammalian cells and highlights the breadth of applica

elegans and mammalian cells and highlights the breadth of applications of this technology.”
“Background Many investigators have suggested that malaria infection predisposes individuals to bacteraemia. We tested this hypothesis with mendelian randomisation studies of children with

the malaria-protective phenotype of sickle-cell trait (HbAS).

Methods This study was done in a defined area around Kilifi District Hospital, Kilifi, Kenya. We did a matched case-control study to identify risk factors for invasive bacterial disease, in which cases were children aged 3 months to 13 years who were admitted to hospital with bacteraemia between Sept 16, 1999, and July 31, 2002. We aimed to match two controls, by Selisistat age, sex, location, and time of recruitment, for every case. We then did a longitudinal case-control study to assess the relation between HbAS and invasive bacterial disease as malaria incidence decreased. Cases were children aged 0-13 years who were admitted to hospital with bacteraemia between Jan 1, 1999, and Dec 31, 2007. Controls were born in the study area between Jan 1, 2006, and June 23, 2009. Finally, we modelled the annual incidence of bacteraemia against the community prevalence of malaria during 9 years with Poisson regression.

Results In the matched case-control study, we recruited 292 cases-we recruited two controls for 236, and one for the remaining

56. Sickle-cell disease, HIV, leucocyte haemozoin pigment, and undernutrition were positively

associated with bacteraemia and HbAS was strongly negatively associated with bacteraemia (odds ratio 0.36; 95% CI 0.20-0.65). BAY 11-7082 manufacturer In the longitudinal case-control study, we assessed data from 1454 cases and 10 749 controls. During the study period, the incidence of admission to hospital with malaria per 1000 child-years decreased from 28.5 to 3.45, with a reduction in protection afforded by HbAS against bacteraemia occurring in parallel (p=0.0008). The incidence of hospital admissions for bacteraemia per 1000 child-years also decreased from 2.59 to 1.45. The bacteraemia incidence rate ratio associated with malaria parasitaemia AZD5582 in vitro was 6.69 (95% CI 1.31-34.3) and, at a community parasite prevalence of 29% in 1999, 62% (8.2-91) of bacteraemia cases were attributable to malaria.

Interpretation Malaria infection strongly predisposes individuals to bacteraemia and can account for more than half of all cases of bacteraemia in malaria-endemic areas. Interventions to control malaria will have a major additional benefit by reducing the burden of invasive bacterial disease.”
“Background. Cognitive models suggest that distress associated with auditory hallucinations is best understood in terms of beliefs about voices. What is less clear is what factors govern such beliefs. This study aimed to explore the way in which traumatic life events contribute towards beliefs about voices and any associated distress.

Method.

Adult male Wistar rats were

subjected to 21 days of restr

Adult male Wistar rats were

subjected to 21 days of restraint stress followed by housing in either standard or enriched BMS202 cell line conditions (10 days, 6 h/day). Survival and differentiation of BrdU-labeled cells were evaluated 31 days post-BrdU administration. Stress decreased the survival and differentiation of progenitor cells, which was ameliorated by EE. Also the percentage of BrdU-ir cells that did not co-localize with NeuN or S100 beta was significantly greater in the stressed rats and was restored by EE. Stress increased immobility in FST and decreased sucrose preference in the SCT, and these behaviors were ameliorated by EE. Adult neurogenesis is thought to be linked to learning and memory and in mediating antidepressant effect. Taken together with our earlier report that EE restores stress-induced impairment in learning and cytogenesis, the Current results indicate that the reversal of adult neurogenesis could be one of the mechanisms involved in the amelioration of stress-induced deficits. (C) 2009 C188-9 ic50 Elsevier Ireland Ltd. All rights reserved.”
“Clinical evidence links increased aortic collagen content and stiffness to abdominal aortic aneurysm (AAA) formation. However, the possibility that excess collagen contributes to AAA formation remains untested. We investigated the hypothesis that augmented

collagen promotes AAA formation, and employed apoE-null mice expressing collagenase-resistant mutant collagen (Col(R/R)/apoE(-/-)),

heterozygote (Col(R/+)/apoE(-/-)), or wild-type collagen (Col(+/+)/apoE(-/-)) infused with angiotensin II to induce AAA. As expected, the aortas of Col(R/R)/apoE(-/-) mice contained more PLK inhibitor interstitial collagen than those from the other groups. Angiotensin II treatment elicited more AAA formation in Col(R/R)/apoE(-/-) mice than Col(R/+)/apoE(-/-) or Col(R/R)/apoE(-/-) mice. Aortic circumferences correlated positively with collagen content, determined by picrosirius red and Masson trichrome staining. Mechanical testing of aortas of Col(R/R)/apoE(-/-) mice showed increased stiffness and susceptibility to mechanical failure compared to those of Col(+/+)/apoE(-/-) mice. Optical analysis further indicated altered collagen fiber orientation in the adventitia of Col(R/R)/apoE(-/-) mice. These results demonstrate that collagen content regulates aortic biomechanical properties and influences AAA formation.”
“Apolipoprotein D (apoD), a member of the lipocalin family of transporter proteins binds a number of small lipophilic molecules including arachidonic acid and cholesterol. Recent studies showed a protective function of mammalian apoD as well as its insect and plant homologs against oxidative stress.

We propose that a lack of energy after TBI caused by inhibition o

We propose that a lack of energy after TBI caused by inhibition of CcO is an important aspect of trauma pathology. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Dysregulation of matrix metalloproteinase (MMP)-2 in the vasculature has been suggested to be associated with increased prevalence of cardiovascular disease and renal injury. In this descriptive study, we hypothesized that arterial MMP-2 activity is elevated in the presence of cardiovascular risk factors such as diabetes, hypertension, smoking and ageing, and that it correlates with the degree of kidney function. MMP-2 activity in internal mammary arteries (n = 37) was measured using gelatinolytic

zymography, and cutoffs click here were determined using sample-derived medians. Patient demographics and clinical data were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated. High MMP-2 activity

(1 60,000 units) was associated with age, hypertension and diabetes (p = 0.0034, 0.06 and 0.0034, respectively). Multivariate analysis showed that age and diabetes were independent predictors of high MMP-2 activity. There is a trend towards increased MMP-2 activity and reduced eGFR (p = 0.010). The current exploratory work describes that the activity of MMP-2 in the internal mammary artery is correlated with age, hypertension, diabetes and eGFR. It is the first report suggesting that MMP-2 in the arterial vasculature could be the Entinostat cell line possible mediator crucial in linking the progression of MG-132 mouse kidney function to cardiovascular disease. Copyright (C) 2008 S. Karger AG, Basel.”
“Thyroid hormones (THs) are well known for their genomic effects but recently attention has focused also on their nongenomic actions as rapid modulators of membrane receptors. Here we show that thyroxine (T4) and 3,3′,5′-L-triiodothyronine (T3) rapidly decrease N-methyl-D-aspartate (NMDA)-evoked currents in rat hippocampal cultures with potency in the micromolar range. The effect is not mediated by glutamate or glycine binding sites as an increase

in agonist or glycine concentration does not alter TH potencies. Furthermore THs’ effect on NMDA receptors is independent of voltage and of subunit composition. The mechanism of THs’ antagonistic effect does not involve PKC phosphorylation of NMDA receptors since neither blocking nor stimulating PKC changed THs’ modulation. T3, but not T4, inhibits also kainate-evoked currents in hippocampal neurons in culture. In hippocampal pyramidal neurons in slice, T3, but not T4, significantly reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without affecting their amplitude and decay. In cultured rat cortical neurons THs prevented glutamate-induced neuronal death at concentrations similar to those effective on glutamatergic receptors.