Biology subjects

Oliveira, S. F.

Publications and source records attributed to Oliveira, S. F..

3 recordsLinked to original sources

bioRxiv2025

Muscle-specific increased expression of JAG1 improves skeletal muscle phenotype in dystrophin-deficient mice.

Therapeutic strategies for Duchenne Muscular Dystrophy (DMD) will likely require complementary approaches. One possibility is to explore genetic modifiers that improve muscle regeneration and function. The beneficial effects of the overexpression of Jagged-1 were described in escaper golden retriever muscular dystrophy (GRMD) dogs that had a near-normal life and validated in dystrophin-deficient zebrafish (1). To clarify the underlying biology of JAG1 overexpression in dystrophic muscles, we generated a transgenic mouse (mdx5cv-JAG1) model that lacks dystrophin and overexpresses human JAG1 in striated muscles. Skeletal muscles from mdx5cv-JAG1 and mdx5cv mice were studied at one, four, and twelve-month time points. JAG1 expression in mdx5cv-JAG1 increased by three to five times compared to mdx5cv. Consequently, mdx5cv-JAG1 muscles were significantly bigger and stronger than dystrophic controls, along with an increased number of myofibers. Proteomics data show increased dysferlin in mdx5cv-JAG1 muscles and an association of Nsd1 with the phenotype. Our data supports the positive effect of JAG1 overexpression in dystrophic muscles. Significance StatementDuchenne Muscular Dystrophy (DMD) patients present a progressive decline in motor function. DMD is caused by mutations in the DMD gene that lead to the absence of dystrophin - an essential component of muscle cells. However, dystrophin-deficient dogs overexpressing JAG1 had a normal lifespan with remarkable motor function. In this study, we increased expression of human JAG1 in mouse skeletal muscles lacking dystrophin to explore mechanisms responsible for these benefits. Our observations show that overexpression of JAG1 counterbalances the lack of dystrophin by generating bigger and stronger muscles as the mouse ages. Moreover, our proteomics dataset suggests a role of dysferlin in the phenotype. Therefore, our study supports the exploration of JAG1 in pre-clinical models.

physiology↗

bioRxiv2024

The influence of sensory noise, confidence judgments, and accuracy on pupil responses and trial-by-trial reaction time adjustments in young and older people

We investigated the association between pupil responses, decision confidence and decision accuracy, their relationship with behavioural adjustments important for optimal task performance, and if these were altered in older adults. We tested young and older adults, including men and women, with a dot motion direction discrimination task, while measuring task-related pupil responses. Feedback was provided after each trial. Participants were instructed to report perceived motion direction and simultaneously their decision confidence. Older adults were overconfident in the presence of high sensory noise and in incorrect trials. Young peoples pupil responses reflected performance lapses. This effect was reduced in older people that showed blunted pupil responses to lapses and to negative feedback. Low confidence, errors, and larger pre-feedback pupil responses were associated with slower reaction time on the subsequent trial. The effects of errors and pupil were stronger in the older group. In conclusion, older peoples blunted pupil responses following lapses suggest reduced awareness of their own abilities and internal brain state and might impair adjustment of behaviour for optimal performance.

neuroscience↗

bioRxiv2019

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.\n\nHighlightsO_LIKetamine induces mixed effects in animal anxiety tests\nC_LIO_LIFew studies investigated the individual effects of S-ketamine in anxiety/fear tests\nC_LIO_LINone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors\nC_LIO_LISystemic ketamine does not affect panic-like behaviors in the elevated T-maze\nC_LI

animal behavior and cognition↗