75 research outputs found
Convergence of IP-based and optical transport networks
Today Network and Service Providers are aware of the increasing data traffic volumes and as such they are strategically moving investigations toward a single integrated voice and data infrastructure. In this context IP is gaining the role of the integration layer for multiple services. Nevetheless incumbent NSPs that build a multi-service IP network are going to need connectivity to its preexisting legacy networks (e.g. ATM. SONET, SDH). This reason motivates the introduction of a client-independent Optical Transport Network (OTN) as a missing link to guarantee a smooth evolution from legacy networks to a data-centric OTN. The scope of this paper is to give some guidelines about the definition of functionality and architectures of a multilayers infrastructure supporting the transport of data and circuit-based services. Particularly, the identification of the different service requirements, as well as the understanding of the allowed degradation, provide a picture of the needed survivability mechanism of IP over OTN scenarios
Chronic Stress Exposure Reduces Parvalbumin Expression in the Rat Hippocampus through an Imbalance of Redox Mechanisms : Restorative Effect of the Antipsychotic Lurasidone
Background
Psychiatric disorders are associated with altered function of inhibitory neurotransmission within the limbic system, which may be due to the vulnerability of selective neuronal subtypes to challenging environmental conditions, such as stress. In this context, parvalbumin-positive GABAergic interneurons, which are critically involved in processing complex cognitive tasks, are particularly vulnerable to stress exposure, an effect that may be the consequence of dysregulated redox mechanisms.
Methods
Adult Male Wistar rats were subjected to the chronic mild stress procedure for 7 weeks. After 2 weeks, both control and stress groups were further divided into matched subgroups to receive chronic administration of vehicle or lurasidone (3 mg/kg/d) for the subsequent 5 weeks. Using real-time RT-PCR and western blot, we investigated the expression of GABAergic interneuron markers and the levels of key mediators of the oxidative balance in the dorsal and ventral hippocampus.
Results
Chronic mild stress induced a specific decrease of parvalbumin expression in the dorsal hippocampus, an effect normalized by lurasidone treatment. Interestingly, the regulation of parvalbumin levels was correlated to the modulation of the antioxidant master regulator NRF2 and its chaperon protein KEAP1, which were also modulated by pharmacological intervention.
Conclusions
Our findings suggest that the susceptibility of parvalbumin neurons to stress may represent a key mechanism contributing to functional and structural impairments in specific brain regions relevant for psychiatric disorders. Moreover, we provide new insights on the mechanism of action of lurasidone, demonstrating that its chronic treatment normalizes chronic mild stress-induced parvalbumin alterations, possibly by potentiating antioxidant mechanisms, which may ameliorate specific functions that are deteriorated in psychiatric patients
Testing the Generalist-Specialist Dilemma: The Role of Pyrrolizidine Alkaloids in Resistance to Invertebrate Herbivores in Jacobaea Species
Chronic mild stress-induced alterations of local protein synthesis: a role for cognitive impairment
Depression, a major cause of disability worldwide, is characterized by a complex and heterogeneous symptomatology. With this respect, cognitive deterioration represents a major problem that has a strong impact on patient's function. Thus, within the context of a depressive phenotype, it is important to characterize the mechanisms that sustain cognitive dysfunctions and may represent an important target for pharmacological intervention. Here, using the chronic mild stress (CMS) paradigm of depression, we found that, independently from the anhedonic phenotype, CMS rats showed a deficit in the novel object recognition (NOR) test, which is associated with an inability to phosphorylate GluN2B subunit on Ser1303 and to activate the mTOR pathway. In agreement with the role of these systems in the control of local protein synthesis, we observed an increase phosphorylated of the eukaryotic Elongation Factor 2 (eEF2) in the crude synaptosomal fraction after the NOR test specifically in control animals. Since it has been demonstrated that peEF2 leads to the translation of specific mRNAs, we investigated if the gene-specific translational control depends on the presence of uORFs. Interestingly, we found a significant increase of oligophrenin-1 (2 uORFs) and of Bmal1 (7 uORFs) protein levels specifically in the control animals exposed to the NOR test. Our results demonstrated that the cognitive decline associated with stress exposure might be due to alterations in local protein translation of specific mRNAs, suggesting that a pharmacological intervention able to correct these defects might be useful in the improvement of deteriorated functions in patients with major depression and stress-related disorders
P.024 Dopamine receptors in prefrontal cortex mediate effects of venlafaxine, but not DBS, in animal models of treatment-responsive and treatment-resistant depression
Effect of lurasidone treatment on chronic mild stress-induced behavioural deficits in male rats: The potential role for glucocorticoid receptor signalling
Background: Stress represents one of the main precipitating factors for psychiatric diseases, characterised by an altered function of glucocorticoid receptors (GR), known to play a role in mood and cognitive function. We investigated the ability of the antipsychotic lurasidone to modulate the involvement of genomic and non-genomic GR signalling in the behavioural alterations due to chronic stress exposure Methods: Male Wistar rats were exposed to seven weeks of chronic mild stress (CMS) and treated with lurasidone (3 mg/kg/day) starting from the second week of stress for more five weeks. Gene expression and protein analyses were conducted in dorsal hippocampus. Results: Seven weeks of CMS induced anhedonia and cognitive impairment, which were normalised by lurasidone. At molecular level, CMS rats showed an increase of GR protein levels by 60% (p<0.001 vs. CTRL/VEH) in the membrane compartment, which was paralleled by an up-regulation of phosphoSINAPSYN Ia/b by 88% (p<0.01 vs. CTRL/VEH) and of the mitochondrial marker Cox3 by 21% (p<0.05 vs. CTRL/VEH). Moreover, while exposure to the novel object recognition test increased the nuclear translocation of GRs by 96% (p<0.01 vs. CTRL/VEH/Na\uefve) and their transcriptional activity in non-stressed rats, such mechanisms were impaired in CMS rats. Interestingly, the genomic and non-genomic alterations of GR, induced by CMS, were normalised by lurasidone. Conclusion: Our results further support the role of glucocorticoid signalling in the dysfunction associated with stress exposure. We provide novel insights on the mechanism of lurasidone, suggesting its effectiveness on different domains associated with psychiatric disorders
PIN83 Cost-Effectiveness and Cost-Utility analysis of 200 Days Prophylaxis of Cytomegalovirus (CMV) infections in High Risk (D+/R-) Kidney Transplant Recipients in Poland
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