Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1. Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand–receptor interactions

The Care of Elderly People in Vietnam

The population ageing as an unprecedented phenomenon in the history of the humanity was considered. It is slow, but persistent and, according to the opinion of the experts, it is irreversible, at least for the next hundred years. Population ageing has a profound impact on economic growth, investment and labor market, the welfare of every citizen of any country. Changes in the structure of the population in terms of aging concerns every person, society, country and the international community. The increase in the number of elderly people determines the necessity of working out new strategies for the stable development of each country in the world. Vietnam is no exception in this case. Population ageing is a contemporary challenge for the worldwide society. It requires the development of the effective strategic and tactic decisions and new systems of care for elder people, aimed at transformation of the population ageing challenges into opportunities, which provide people’s welfare. The main aim of the study is to determine the ways of perfection of the care system of the Vietnamese older people. The methods: system analysis of statistic data about the demographic structure of the Vietnamese population and the morbidity structure of the Vietnamese seniors; situation analyses. The results: specific features and conditions of the system of care of elderly people in Vietnam are studied. The analysis of the main factors that affect the system of care of the older people is conducted. The conclusions and proposals to enhance the system of care of the older people are drawn

Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training

Gene transcription and translation in the hippocampus is of critical importance in hippocampus-dependent memory formation, including during Morris water maze (MWM) learning. Previous work using gene deletion models has shown that the immediate-early genes (IEGs) c-Fos, Egr-1 and Arc are crucial for such learning. Recently, we reported that induction of IEGs in sparse dentate gyrus neurons requires ERK MAPK signaling and downstream formation of a distinct epigenetic histone mark (i.e. phospho-acetylated histone H3). Until now, this signaling, epigenetic and gene transcriptional pathway has not been comprehensively studied in the MWM model. Therefore, we conducted a detailed study of the phosphorylation of ERK1/2 and serine10 in histone H3 (H3S10p) and induction of IEGs in the hippocampus of MWM trained rats and matched controls. MWM training evoked consecutive waves of ERK1/2 phosphorylation and H3S10 phosphorylation, as well as c-Fos, Egr-1 and Arc induction in sparse hippocampal neurons. The observed effects were most pronounced in the dentate gyrus. A positive correlation was found between the average latency to find the platform and the number of H3S10p-positive dentate gyrus neurons. Furthermore, chromatin immuno-precipitation (ChIP) revealed a significantly increased association of phospho-acetylated histone H3 (H3K9ac-S10p) with the gene promoters of c-Fos and Egr-1, but not Arc, after MWM exposure compared with controls. Surprisingly, however, we found very little difference between IEG responses (regarding both protein and mRNA) in MWM-trained rats compared with matched swim controls. We conclude that exposure to the water maze evokes ERK MAPK activation, distinct epigenetic changes and IEG induction predominantly in sparse dentate gyrus neurons. It appears, however, that a specific role for IEGs in the learning aspect of MWM training may become apparent in downstream AP-1- and Egr-1-regulated (second wave) genes and Arc-dependent effector mechanisms

Negative Feedback Regulation following Administration of Chronic Exogenous Corticosterone

Administration of exogenous glucocorticoids is known to suppress the HPA axis and has been reported to occupy brain glucocorticoid receptors, eventually leading to down-regulation. To determine the effects of chronic corticosterone administration on HPA axis function, corticosterone was administered as both 25% and 50% corticosteronekholesterol pellets. Rats were sacrificed 6 days after corticosterone pellet implantation. The 25% corticosterone pellets produced a small increase in morning corticosterone concentrations but no change in evening ACTH or corticosterone secretion. The 50% corticosterone pellets produced constant corticosterone concentrations of 5–6 pg/dl, with no circadian variation in corticosterone, indicating inhibition of evening ACTH and corticosterone secretion. The 25% corticosterone pellets produced no significant decrease in thymus weight or in adrenal weight; 50% corticosterone pellets produced significant decreases in thymus weight and adrenal weight. Neither 25% nor 50% corticosterone pellets produced significant decreases in GR in hippocampus and cortex. The 50% corticosterone pellets treatment resulted in a decrease in anterior pituitary POMC mRNA levels, a decrease in baseline and oCRH stimulated ACTH release from the anterior pituitary, and a near complete inhibition of the AM and PM response to restraint stress. These results suggest that: 1) the HPA axis was able to adjust to the small increase in glucocorticoids produced by the 25% cort pellets with minimal disturbances in function and 2) 50% corticosterone pellets exert a significant inhibitory effect on stress and diurnal ACTH secretion which appears to be exerted at the pituitary as well as possible inhibitory effects on brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72571/1/j.1365-2826.1995.tb00665.x.pd

Феномен мема в цифровом обществе как предмет осмысления: социально-философский анализ

Глобальная трансформация цифрового общества сопровождается не только проникновением интернет-коммуникации во все сферы жизнедеятельности общества, но и глубоким переосмыслением коммуникативной природы социальной реальности. Коммуникации сегодня - это общий мир значимых объектов и событий, наши чувства и мысли, наши способы выражения этих социально выстраиваемых реальностей формируют коммуникативное пространство.The global transformation of the digital society is accompanied not only by the penetration of Internet communication into all spheres of society, but also by a deep rethinking of the communicative nature of social reality. Communication today is a common world of significant objects and events, our feelings and thoughts, our ways of expressing these socially constructed realities form a communicative space

Piccole capitali creative

Nel secolo urbano che abbiamo di fronte, la citt\ue0 sar\ue0 lo scenario della competizione delle energie, delle risorse umane, delle intelligenze collettive e della creativit\ue0 per la costruzione di un\u2019evoluzione pi\uf9 compatibile con le identit\ue0 e le vocazioni e pi\uf9 sostenibile rispetto alle risorse ed alle sensibilit\ue0 del territorio. I segnali delle sue forme, delle sue relazioni e delle sue identit\ue0 sono gi\ue0 evidenti in alcune citt\ue0 del presente ed ad essi sono dedicate numerose ricerche urbanistiche, sociologiche ed economiche. Ma i segnali sono evidenti e trasmettono ispirazioni e stimoli anche a chi osserva la citt\ue0 per mestiere di progettista, di pianificatore, di stratega dello sviluppo. Il XXI secolo sar\ue0 l\u2019era indiscussa delle citt\ue0 e su di esse si misurer\ue0 lo sviluppo delle nazioni. Per la prima volta, pi\uf9 della met\ue0 della popolazione mondiale vivr\ue0 nelle citt\ue0, in Europa oggi la cifra \ue8 gi\ue0 di oltre il 75%, e nei paesi in via di sviluppo raggiunger\ue0 velocemente il 50%. Il mondo si svilupper\ue0 sia attorno a grandi megalopoli da decine di milioni di abitanti, ma anche attorno a citt\ue0 metropolitane, a conurbazioni diffuse e ad armature di micropoli: all\u2019armatura urbana delle citt\ue0 globali si annoder\ue0, soprattutto in Europa, l\u2019armatura delle citt\ue0 di secondo livello, produttrici di visioni alternative rispetto all\u2019esplosione delle megalopoli. L\u2019armatura urbana europea di secondo livello \u2013 le piccole capitali, sempre pi\uf9 citt\ue0-porta \u2013 si delinea come annodata attorno a \u201ccitt\ue0 della cultura\u201d, nel senso di citt\ue0 non solo detentrici di risorse culturali profonde lasciate dal palinsesto della storia, ma anche produttrici di nuova cultura: le culture-based competition cities saranno, infatti, quelle citt\ue0 in grado di competere nel panorama internazionale attraverso la valorizzazione e la promozione della propria identit\ue0 culturale, sia consolidata che in evoluzione