Chronic Stress Triggers Expression of Immediate Early Genes and Differentially Affects the Expression of AMPA and NMDA Subunits in Dorsal and Ventral Hippocampus of Rats

Indexación: Web of Science; Scopus.Previous studies in rats have demonstrated that chronic restraint stress triggers anhedonia, depressive-like behaviors, anxiety and a reduction in dendritic spine density in hippocampal neurons. In this study, we compared the effect of repeated stress on the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits in dorsal and ventral hippocampus (VH). Adult male Sprague-Dawley rats were randomly divided into control and stressed groups, and were daily restrained in their motion (2.5 h/day) during 14 days. We found that chronic stress promotes an increase in c-Fos mRNA levels in both hippocampal areas, although it was observed a reduction in the immunoreactivity at pyramidal cell layer. Furthermore, Arc mRNAs levels were increased in both dorsal and VH, accompanied by an increase in Arc immunoreactivity in dendritic hippocampal layers. Furthermore, stress triggered a reduction in PSD-95 and NR1 protein levels in whole extract of dorsal and VH. Moreover, a reduction in NR2A/NR2B ratio was observed only in dorsal pole. In synaptosomal fractions, we detected a rise in NR1 in dorsal hippocampus (DH). By indirect immunofluorescence we found that NR1 subunits rise, especially in neuropil areas of dorsal, but not VH. In relation to AMPA receptor (AMPAR) subunits, chronic stress did not trigger any change, either in dorsal or ventral hippocampal areas. These data suggest that DH is more sensitive than VH to chronic stress exposure, mainly altering the expression of NMDA receptor (NMDAR) subunits, and probably favors changes in the configuration of this receptor that may influence the function of this area.https://www.frontiersin.org/articles/10.3389/fnmol.2017.00244/ful

The ROCK inhibitor Fasudil prevents chronic restraint stress-induced depressive-like behaviors and dendritic spine loss in rat hippocampus

Indexación: Web of Science; Scopus.Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase. We have reported that chronic stress promotes depressive-like behaviors in rats along with dendritic spine loss in apical dendrites of hippocampal pyramidal neurons, changes associated with Rho kinase activation. The present study proposes that the Rho kinase inhibitor Fasudil may prevent the stress-induced behavior and dendritic spine loss. Methods: Adult male Sprague-Dawley rats were injected with saline or Fasudil (i.p., 10 mg/kg) starting 4 days prior to and maintained during the restraint stress procedure (2.5 h/d for 14 days). Nonstressed control animals were injected with saline or Fasudil for 18 days. At 24 hours after treatment, forced swimming test, Golgi-staining, and immuno-western blot were performed. Results: Fasudil prevented stress-induced immobility observed in the forced swimming test. On the other hand, Fasudiltreated control animals showed behavioral patterns similar to those of saline-treated controls. Furthermore, we observed that stress induced an increase in the phosphorylation of MYPT1 in the hippocampus, an exclusive target of Rho kinase. This change was accompanied by dendritic spine loss of apical dendrites of pyramidal hippocampal neurons. Interestingly, increased pMYPT1 levels and spine loss were both prevented by Fasudil administration. Conclusion: Our findings suggest that Fasudil may prevent the development of abnormal behavior and spine loss induced by chronic stress by blocking Rho kinase activity.https://academic.oup.com/ijnp/article/20/4/336/263217

MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology

Indexación: Scopus.1Laboratory of Neuroplasticity and Neurogenetics, Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, Universidad de Chile, Santiago, Chile, 2National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, NC, United States, 3Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago, Chile, 4Millennium Institute for Integrative Biology (iBio), FONDAP Center for Genome Regulation, Departamento de Genética Molecular y Microbiología, Pontificia Universidad Católica de Chile, Santiago, Chile, 5Department of Kinesiology, Faculty of Health Sciences, Universidad Católica del Maule, Talca, Chile, 6Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.This study was supported by the following grants: FONDECYT 1120528 (JLF), Fondo Central de Investigación, Universidad de Chile ENL025/16 (JLF), ES090079 (JAC). Research in RG and EV laboratories is funded by Instituto Milenio iBio – Iniciativa Científica Milenio MINECON.Studies conducted in rodents subjected to chronic stress and some observations in humans after psychosocial stress, have allowed to establish a link between stress and the susceptibility to many complex diseases, including mood disorders. The studies in rodents have revealed that chronic exposure to stress negatively affects synaptic plasticity by triggering changes in the production of trophic factors, subunit levels of glutamate ionotropic receptors, neuron morphology, and neurogenesis in the adult hippocampus. These modifications may account for the impairment in learning and memory processes observed in chronically stressed animals. It is plausible then, that stress modifies the interplay between signal transduction cascades and gene expression regulation in the hippocampus, therefore leading to altered neuroplasticity and functioning of neural circuits. Considering that miRNAs play an important role in post-transcriptional-regulation of gene expression and participate in several hippocampus-dependent functions; we evaluated the consequences of chronic stress on the expression of miRNAs in dorsal (anterior) portion of the hippocampus, which participates in memory formation in rodents. Here, we show that male rats exposed to daily restraint stress (2.5 h/day) during 7 and 14 days display a differential profile of miRNA levels in dorsal hippocampus and remarkably, we found that some of these miRNAs belong to the miR-379-410 cluster. We confirmed a rise in miR-92a and miR-485 levels after 14 days of stress by qPCR, an effect that was not mimicked by chronic administration of corticosterone (14 days). Our in silico study identified the top-10 biological functions influenced by miR-92a, nine of which were shared with miR-485: Nervous system development and function, Tissue development, Behavior, Embryonic development, Organ development, Organismal development, Organismal survival, Tissue morphology, and Organ morphology. Furthermore, our in silico study provided a landscape of potential miRNA-92a and miR-485 targets, along with relevant canonical pathways related to axonal guidance signaling and cAMP signaling, which may influence the functioning of several neuroplastic substrates in dorsal hippocampus. Additionally, the combined effect of miR-92a and miR-485 on transcription factors, along with histone-modifying enzymes, may have a functional relevance by producing changes in gene regulatory networks that modify the neuroplastic capacity of the adult dorsal hippocampus under stress. © 2018 Muñoz-Llanos, García-Pérez, Xu, Tejos-Bravo, Vidal, Moyano, Gutiérrez, Aguayo, Pacheco, García-Rojo, Aliaga, Rojas, Cidlowski and Fiedler.https://www.frontiersin.org/articles/10.3389/fnmol.2018.00251/ful

A visual programming model to implement coarse-grained DSP applications on parallel and heterogeneous clusters

International audienceThe digital signal processing (DSP) applications are one of the biggest consumers of computing. They process a big data volume which is represented with a high accuracy. They use complex algorithms, and must satisfy a time constraints in most of cases. In the other hand, it's necessary today to use parallel and heterogeneous architectures in order to speedup the processing, where the best examples are the su-percomputers "Tianhe-2" and "Titan" from the top500 ranking. These architectures could contain several connected nodes, where each node includes a number of generalist processor (multi-core) and a number of accelerators (many-core) to finally allows several levels of parallelism. However, for DSP programmers, it's still complicated to exploit all these parallelism levels to reach good performance for their applications. They have to design their implementation to take advantage of all heteroge-neous computing units, taking into account the architecture specifici-ties of each of them: communication model, memory management, data management, jobs scheduling and synchronization . . . etc. In the present work, we characterize DSP applications, and based on their distinctive-ness, we propose a high level visual programming model and an execution model in order to drop down their implementations and in the same time make desirable performances

Undamning the Douro river catchment: a stepwise approach for prioritizing dam removal

Dams provide water supply, flood protection, and hydropower generation benefits, but also harm native species by altering the natural flow regime, and degrading the aquatic and riparian habitats. In the present study, which comprised the Douro River basin located in the North of Portugal, the cost-benefit assessment of dams was based upon a balance between the touristic benefits of a dammed Douro, and the ecological benefits of less fragmented Douro sub-catchments. Focused on four sub-catchments (Sabor, Tâmega, Côa and Corgo), a probabilistic stream connectivity model was developed and implemented to recommend priorities for dam removal, where this action could significantly improve the movement of potadromous fish species along the local streams. The proposed model accounts for fish movement across the dam or weir (permeability), which is a novel issue in connectivity models. However, before any final recommendation on the fate of a dam or weir, the connectivity results will be balanced with other important socio-economic interests. While implementing the connectivity model, an inventory of barriers (dams and weirs) was accomplished through an observation of satellite images. Besides identification and location of any obstacles, the inventory comprised the compilation of data on surrounding land use, reservoir water use, characteristics of the riparian gallery, and permeability conditions for fish, among others. All this information was stored in a geospatial dataset that also included geographical information on the sub-catchment drainage network. The linear (drainage network) and point (barriers) source data were processed in a computer program that provided or returned numbers for inter-barrier stream lengths (habitat), and the barrier permeability. These numbers were finally used in the same computer program to calculate a habitat connector index, and a link improvement index, used to prioritize dam removal based upon structural connectivity criteria. The results showed that habitat patch connectivity in the Sabor, Tâmega and Côa sub-catchments is not dramatically affected by the installed obstacles, because most link improvement values were generally low. For the opposite reason, in the Corgo sub-catchment, obstacles may constitute a relatively higher limitation to connectivity, and in this case the removal of eight obstacles could significantly improve this connectivity. Using the probabilistic model of structural connectivity, it was possible to elaborate a preliminary selection of dams/weirs that critically limit stream connectivity, and that will be the focus of field hydraulic characterization to precisely determine fish movement along the associated river stretches. Future work will also include the implementation of a multi-criteria decision support system for dam removal or mitigation of the critical structures, as well to define exclusion areas for additional obstaclesinfo:eu-repo/semantics/publishedVersio

Type II compactifications on manifolds with SU(2) x SU(2) structure

We study compactifications of type II theories on SU(2) x SU(2) structure manifolds to six, five and four spacetime dimensions. We use the framework of generalized geometry to describe the NS-NS sector of such compactifications and derive the structure of their moduli spaces. We show that in contrast to SU(3) x SU(3) structure compactifications, there is no dynamical SU(2) x SU(2) structure interpolating between an SU(2) structure and an identity structure. Furthermore, we formulate type II compactifications on SU(2) x SU(2) structures in the context of exceptional generalized geometry which makes the U-duality group manifest and naturally incorporates the scalar degrees of freedom arising in the Ramond-Ramond sector. Via this formalism we derive the structure of the moduli spaces as it is expected from N=4 supergravity.Comment: 69 pages, v2 published versio

Consistency of the mass variation formula for black holes accreting cosmological fluids

We address the spherical accretion of generic fluids onto black holes. We show that, if the black hole metric satisfies certain conditions, in the presence of a test fluid it is possible to derive a fully relativistic prescription for the black hole mass variation. Although the resulting equation may seem obvious due to a form of it appearing as a step in the derivation of the Schwarzschild metric, this geometrical argument is necessary to fix the added degree of freedom one gets for allowing the mass to vary with time. This result has applications on cosmological accretion models and provides a derivation from first principles to serve as a base to the accretion equations already in use in the literature.Comment: 4 pages, 1 figure. To appear in Gen. Rel. Gra