Localization of Mineralocorticoid Receptors at Mammalian Synapses

In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids

Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms

Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug—yohimbine, and an anti-anxiety drug—diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain–blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders—notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders and schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap with schizophrenia. PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain

Technologia obróbki Water-Jet i możliwości jej zastosowania

The paper is dealing with the environmental research of waste material rising from abrasive water-jet cutting. On the occasion of disposal of the slurry from the overfull collector tank in the Laboratory of the Liquid jet of the Department of Physics at the Technical University of Ostrava the waste material was studied. Samples from different points of the catcher were collected into the beaks, dried up and consequently their elemental and structural composition has been analyzed. The results were primarily evaluated from the viewpoint of effectiveness of further abrasive recycling and usage (either as an abrasive - for this reason the residual cutting ability of the grains was discussed, or as a fine powder material for other applications – the size and shape of the grains was considered). Second viewpoint which was discussed was potential environmental hazard arising from the normal disposal of the waste material. The analysis of dried slurry samples was carried on by electron microprobe. Twenty one samples of waste mixture from various parts and depths of the tank were analyzed and compared with samples of non-used abrasive material. It was proved that abrasive material which had undergone the process of cutting was significantly impaired. It should be recycled in some cases but careful economic calculation taking into account all additional costs connected with separation of suitable abrasive fraction and its drying should be necessary. X-rays analysis provided information about chemical composition of the waste material. Most of the sludge was from abrasives, namely almandine. Higher contents of magnesium oxide, lower contents of aluminum oxide and higher contents of iron oxide, however, was probably caused by presence of other abrasive materials, such as olivine or zirconium which had been also used for cutting during the working period of the system. No potentially harmful material was detected by the X-ray analysis. It can be therefore stated that waste material from the water-jet cutting can be disposed on a common landfill without any restrictions.Praca traktuje o badaniu środowiskowym odpadów powstałych po cięciu strumieniem wodno-ściernym (water-jet). Materiał przebadano przy okazji czyszczenia zawiesiny z przepełnionego zbiornika kolektora w laboratorium prowadzącym badania nad ciekłym strumieniem na Uniwersytecie Technicznym w Ostrawie. Próbki zostały pobrane z różnych punktów zbiornika do zlewek i osuszone. Następnie przeanalizowano ich skład pierwiastkowy i strukturalny. Wyniki przede wszystkim były oceniane pod kątem skuteczności dalszego recyklingu i użytku odpadów ściernych (zarówno jako materiał ścierny – z tego powodu badano zdolności tnące resztek ziaren oraz inne zastosowania tego materiału w postaci drobnego proszku, brano pod uwagę wielkość i kształt ziaren). Drugim aspektem badań było ryzyko środowiskowe wynikające z dotychczasowego sposobu usuwania odpadów. Analizę próbek osuszonej zawiesiny dokonano przy użyciu mikrosondy elektronowej. Poddano analizie 21 próbek mieszaniny odpadów z różnych części i głębokości pojemnika i porównano je z próbkami niezużytego materiału. Wykazano, że materiał ścierny, który był użyty do procesu cięcia został znacząco zniszczony. W niektórych przypadkach powinien zostać poddany recyklingowi, jednakże należy przeprowadzić dokładne wyliczenia ekonomiczne uwzględniające dodatkowe koszty dotyczące separacji części materiału oraz osuszania. Analiza rentgenowska dostarczyła informacji na temat składu chemicznego odpadu. Większość osadu pochodziła z materiałów ściernych, dokładniej almandynu. Niemniej jednak, zwiększone zawartości tlenku magnezu oraz tlenku żelaza i niższe zawartości tlenku glinu były prawdopodobnie spowodowane obecnością innych materiałów ściernych, tj. oliwinu czy cyrkonu, które również zostały wykorzystane do cięcia w czasie pracy. Analiza rentgenowska nie wykazała występowania żadnych potencjalnie niebezpiecznych materiałów. Można zatem stwierdzić, ze odpady powstałe z cięcia strumieniem wodno-ściernym (watrer-jet) można składować na standardowym wysypisku bez żadnych ograniczeń

ENRICHED ENVIRONMENT INFLUENCES HORMONAL STATUS AND HIPPOCAMPAL BRAIN DERIVED NEUROTROPHIC FACTOR IN A SEX DEPENDENT MANNER

The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved