Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation

Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.

     

Post-exercise hypotension following different resistance exercise protocols

Sport Sciences for Health - To investigate the hemodynamic responses, especially HPE following different resistance exercises RE protocols in young adult subjects. Eighty-nine men...     

Is Rhodnius prolixus (Triatominae) invading houses in central Brazil?

Sylvatic triatomines of the genus Rhodnius commonly fly into houses in Latin America, maintaining the risk of Chagas disease transmission in spite of control efforts. In the recent past, adult bugs collected inside houses in central Brazil were identified as R. prolixus, a primary disease vector whose natural geographical range excludes this region. Three nearly sibling species (R. neglectus, R. nasutus, and R. robustus), secondary vectors with limited epidemiological significance, occur naturally south of the Brazilian Amazon. The specific status of Rhodnius specimens found inside houses in central Brazil is therefore an epidemiologically important (and still debated) issue. We used wing and head geometric morphometrics to investigate the taxonomic status of 230 adult specimens representing all four 'R. prolixus group' species (19 populations from palm trees, domiciles, and reference laboratory colonies). Discriminant analyses of shape variation allowed for an almost perfect reclassification of individuals to their putative species. Shape patterning revealed no consistent differences between most specimens collected inside houses in central Brazil and R. neglectus, and showed that R. robustus and R. neglectus occur sympatrically (and fly into houses) in southern Amazonia. Furthermore, all Brazilian specimens clearly differed from our reference R. prolixus population. Using geometric morphometrics, we confidently ascribed individual triatomines to their species within the problematic 'R. prolixus group', illustrating the potential value of this approach in entomological surveillance. Our results strongly support the idea that R. neglectus, and not R. prolixus, is the species invading houses in central Brazil.     

Targeting the Dopaminergic System in Autoimmunity

Journal of Neuroimmune Pharmacology - Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players...     

Human respiratory syncytial virus N,P and M protein interactions in HEK-293T cells

Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed.     

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Stress distribution of different implant connections associated with multiple implant-supported prostheses

Abstract

In some clinical situations, the clinician may encounter previously installed implants that should be associated with other implants for a proper rehabilitation. The aim of this study was to evaluate the biomechanical behaviour of a multiple prosthesis joined by different implant connections using photoelasticity. Photoelastic models with a screwed fixed prosthesis supported by implants with different connection systems (Morse taper, external hexagon, internal hexagon, and Flexcone), and different combinations among them, were fabricated. Each assembly was placed in a circular polariscope, and axial and oblique (45°) loads of 100 N were applied on the occlusal surface of the crowns. The fringe patterns were photographed and the analysis was performed by counting the number of high-intensity fringes and also according to the stress distribution region where they appeared. Among implants of the same connection, the external connections obtained a greater number of high intensity fringes when compared to the internal connections. From the biomechanical point of view, the association between different types of connections obtained positive results.