9 research outputs found

    Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

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    Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system

    Separation and determination of alpha-synuclein monomeric and oligomeric species using two electrophoretic approaches

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    Parkinson's disease (PD) is a frequent degenerative disorder that is diagnosed based on clinical symptoms. When the first symptoms appear, more than 70% of the dopaminergic cells are already lost. Therefore, it is of utmost importance to have reliable biomarkers to diagnose much earlier PD. In this context, alpha-synuclein (aSyn) is a protein of high interest because of its tendency to form oligomers and amyloid fibrils. The oligomeric forms seem to play a critical pathological role in PD. To date, most of studies aiming at detecting and quantifying aSyn oligomers were performed by immunoassays, mainly by ELISA using specific antibodies. In this study a capillary gel electrophoresis (CGE) coupled with fluorescence detection method was developed to detect and quantify the oligomeric forms of aSyn formed in vitro. All the results obtained were supported by SDS–PAGE analysis, a widely used and well-known technique but exhibiting a main drawback since it is not an automated technique. The repeatability and the intermediate precision of the method were evaluated, as well as the stability of the labeled and non-labeled aSyn samples. After careful screening and optimization of various labeling reagents, 4-fluoro-7-nitrobenzofurazan (NBD-F) was selected and used to establish a calibration curve with monomeric fluorescently-labeled aSyn. Finally, the method was used to study the effect of doxycycline on the oligomerization process. Altogether, our results show that CGE is a very promising automated technique to analyze aSyn monomers, as well as small oligomers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

    Optimizing Mass Spectrometry Analyses: A Tailored Review on the Utility of Design of Experiments

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