Biology subjects

Amaral, O. B.

Publications and source records attributed to Amaral, O. B..

11 recordsLinked to original sources

bioRxiv2025

THE HUMAN NEUROBLASTOMA SH-SY5Y CELL LINE AS A MODEL TO ASSESS β-AMYLOID NEUROTOXICITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

The SH-SY5Y human neuroblastoma cell line is widely used as an in vitro model of {beta}-amyloid (A{beta}) neurotoxicity in Alzheimers disease (AD). However, the lack of standardized protocols for assessing A{beta} toxicity - including differentiation strategies for SH-SY5Y cells - limits the comparability of results across studies. To address these issues, we conducted a systematic review and meta-analysis to evaluate how methodological factors influence A{beta}-induced toxicity in SH-SY5Y cells. We included 359 eligible studies encompassing 1,192 MTT-based comparisons of cell viability between A{beta}-treated and control SH-SY5Y cells. A three-level meta-analysis estimated mean cell viability after A{beta} exposure at 63% of control levels (95% CI [61.6; 64.3]), with very high heterogeneity (I{superscript 2}=99.6%). Meta-regression identified significant associations between increased toxicity and higher A{beta} concentrations, longer exposure durations, and the use of peptide preparations described as fibrils. Conversely, differentiation protocols, duration, and cell density did not significantly influence toxicity outcomes. Reporting quality was often poor, with frequent omissions regarding cell line origin, authentication, contamination testing, A{beta} preparation details and nature of the experimental unit. Overall, our findings show robust A{beta} toxicity in SH-SY5Y cells, primarily driven by dose, exposure time, and A{beta} aggregation state, but not cell differentiation status. Our conclusions highlight the critical need for better reporting of A{beta} exposure parameters to enhance reproducibility and translational potential in AD research.

neuroscience↗

bioRxiv2025

Estimating the replicability of Brazilian biomedical science

Concerns over the replicability and reproducibility of published research have grown in many research fields, but empirical data to inform policies are still scarce. Biomedical research in Brazil expanded rapidly over the last three decades, with no systematic assessment of the replicability of its findings. With this in mind, we set up the Brazilian Reproducibility Initiative, a multicenter replication of published experiments from Brazilian science using three common experimental methods: the MTT assay, the reverse transcription polymerase chain reaction (RT-PCR) and the elevated plus maze (EPM). A total of 56 laboratories performed 143 replications of 56 experiments; of these, 90 replications of 45 experiments were considered valid by an independent committee. Replication rates for these experiments varied between 20 and 44% according to five predefined criteria. In median terms, ratios between group means were 58% lower in replications than in original experiments, while coefficients of variation were 82% higher. Effect size decrease was smaller for MTT experiments, original results with less variability and those considered more challenging to replicate, while t values for replications were positively correlated with researcher predictions about replicability, and negatively correlated with the rate of publications by the original articles last author. Deviations from preregistered protocols were very common in replications, most frequently due to reasons inherent to the experimental model or related to infrastructure and logistics. Our results highlight factors that limit the replicability of results published by researchers in Brazil and suggest ways by which this scenario can be improved.

scientific communication and education↗

bioRxiv2022

Mapping the content of comments on bioRxiv and medRxiv preprints

IntroductionPreprints have been increasingly used in biomedical sciences, providing the opportunity for research to be publicly assessed before journal publication. With the increase in attention over preprints during the COVID-19 pandemic, we decided to assess the content of comments left on preprint platforms. MethodsPreprints posted on bioRxiv and medRxiv in 2020 were accessed through each platforms API, and a random sample of preprints that had received between 1 and 20 comments was analyzed. Comments were evaluated in triplicate by independent evaluators using an instrument that assessed their features and general content. Results7.3% of preprints received at least 1 comment during a mean follow-up of 7.5 months. Analyzed comments had a median size of 43 words. Criticisms, corrections or suggestions were the most prevalent type of content, followed by compliments or positive appraisals and questions. Most critical comments regarded interpretation, data collection and methodological design, while compliments were usually about relevance and implications. ConclusionsOnly a small percentage of preprints posted in 2020 in bioRxiv and medRxiv received comments in these platforms. When present, however, these comments address content that is similar to that analyzed by traditional peer review. A more precise taxonomy of peer review functions would be desirable to describe whether post-publication peer review fulfills these roles.

scientific communication and education↗

bioRxiv2022

A meta-analysis of the effect of protein synthesis inhibitors on rodent fear conditioning

Systematic reviews and meta-analyses have been increasingly recognized for their potential value in pre-clinical research, but their applications have not been extensively explored in behavioral neuroscience. In this work, we studied protein synthesis inhibition, a classic intervention used to disrupt fear learning, reconsolidation, and extinction in rodents, to explore how meta-analyses can identify potential moderators of its effect. We initially performed separate meta-analyses for different injection sites and target sessions to evaluate the effect of the intervention in various scenarios. Heterogeneity was further investigated by multilevel meta-regression models aggregating various sites, with article or research group as additional levels. We detected robust effects of protein synthesis inhibitors on training and reconsolidation, but not on extinction, possibly due to the lower number of studies on the latter. Our analyses identified some well-established moderators, such as intervention timing and reexposure duration. However, other factors proposed as boundary conditions for reconsolidation, such as memory age and training strength, were not associated with effect size. While our results point to the value of meta-analyses in consolidating findings from the literature, we believe that associations suggested by data synthesis should ideally be verified by well-powered, rigorous confirmatory experiments.

neuroscience↗

bioRxiv2021

Memory destabilization during reconsolidation - A consequence of homeostatic plasticity?

Remembering is not a static process: when retrieved, a memory can be destabilized and become prone to modifications. This phenomenon has been demonstrated in a number of brain regions, but the neuronal mechanisms that rule memory destabilization and its boundary conditions remain elusive. Using two distinct computational models that combine Hebbian plasticity and synaptic downscaling, we show that homeostatic plasticity can function as a destabilization mechanism, accounting for behavioral results of protein synthesis inhibition upon reactivation with different reexposure times. Furthermore, by performing systematic reviews, we identify a series of overlapping molecular mechanisms between memory destabilization and synaptic downscaling, although direct experimental links between both phenomena remain scarce. In light of these results, we propose a theoretical framework where memory destabilization can emerge as an epiphenomenon of homeostatic adaptations prompted by memory retrieval.

neuroscience↗

bioRxiv2019

Shifting from fear to safety through deconditioning-update: a novel approach to attenuate fear memories

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of \"deconditioning\" animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval. Our results indicate that deconditioning-update is more effective than traditional extinction in reducing fear responses; moreover, such effects are long lasting and resistant to renewal and spontaneous recovery. Remarkably, this strategy overcame important boundary conditions for memory updating, such as remote or very strong traumatic memories. The same beneficial effect was found in other types of fear-related memories. Deconditioning was mediated by L-type voltage-gated calcium channels and is consistent with computational accounts of mismatch-induced memory updating. Our results suggest that shifting from fear to safety through deconditioning-update is a promising approach to attenuate traumatic memories.

neuroscience↗

bioRxiv2019

Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the readers ability to independently interpret data and reproduce findings. MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons between preprints from bioRxiv to their own peer-reviewed versions in journals. ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication. ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions.

scientific communication and education↗

bioRxiv2018

Different temporal windows for contextual fear memory destabilisation in the amygdala and hippocampus

Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent restabilisation. Different molecular mechanisms have been postulated for destabilisation in the amygdala and hippocampus, including CB1 receptor activation, protein degradation and AMPA receptor exchange; however, most of the amygdala studies have used pre-re-exposure interventions, while those in the hippocampus have performed them after re-exposure. To test whether the temporal window for destabilisation is similar across both structures, we trained Lister Hooded rats in a contextual fear conditioning task, and 1 day later performed memory re-exposure followed by injection of either the NMDA antagonist MK-801 (0.1 mg/kg) or saline in order to block reconsolidation. In parallel, we also performed local injections of either the CB1 antagonist SR141716A or its vehicle in the hippocampus or in the amygdala, either immediately before or immediately after reactivation. Infusion of SR141716A in the hippocampus prevented the reconsolidation-blocking effect of MK-801 when performed after re-exposure, but not before it. In the amygdala, meanwhile, pre-reexposure infusions of SR141716A impaired reconsolidation blockade by MK-801, although the time-dependency of this effect was not as clear as in the hippocampus. Our results suggest the temporal windows for CB1-receptor-mediated memory destabilisation during reconsolidation vary between brain structures. Whether this reflects different time windows for engagement of these structures or different roles played by CB1 receptors in destabilisation across structures remains an open question for future studies.

neuroscience↗

bioRxiv2018

Chronic in vivo optogenetic stimulation modulates Hebbian plasticity and spine density in the mouse hippocampus

Prolonged increases in excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely-moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 h of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Lastly, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

neuroscience↗

bioRxiv2017

Effect size and statistical power in the rodent fear conditioning literature - a systematic review

Proposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of experiments. However, it is unclear to what extent these two concepts are indeed taken into account in basic biomedical science. To study this in a real-case scenario, we performed a systematic review of effect sizes and statistical power in studies on learning of rodent fear conditioning, a widely used behavioral task to evaluate memory. Our search criteria yielded 410 experiments comparing control and treated groups in 122 articles. Interventions had a mean effect size of 29.5%, and amnesia caused by memory-impairing interventions was nearly always partial. Mean statistical power to detect the average effect size observed in well-powered experiments with significant differences (37.2%) was 65%, and was lower among studies with non-significant results. Only one article reported a sample size calculation, and our estimated sample size to achieve 80% power considering typical effect sizes and variances (15 animals per group) was reached in only 12.2% of experiments. Actual effect sizes correlated with effect size inferences made by readers on the basis of textual descriptions of results only when findings were non-significant, and neither effect size nor power correlated with study quality indicators, number of citations or impact factor of the publishing journal. In summary, effect sizes and statistical power have a wide distribution in the rodent fear conditioning literature, but do not seem to have a large influence on how results are described or cited. Failure to take these concepts into consideration might limit attempts to improve reproducibility in this field of science.

neuroscience↗

bioRxiv2016

Promiscuity of peripheral molecular biomarkers in major psychiatric disorders: a transdiagnostic systematic review

The search for biomarkers has been one of the leading endeavors in biological psychiatry; nevertheless, in spite of hundreds of publications, it has yet to make an impact in clinical practice. To study how biomarker research has progressed over the years, we performed a systematic review of the literature to evaluate (a) the most studied peripheral molecular markers in major psychiatric disorders, (b) the main features of studies in which they are proposed as biomarkers and (c) whether their patterns of variation are similar across disorders. Out of the six molecules most commonly present as keywords in articles studying plasmatic markers of schizophrenia, major depressive disorder or bipolar disorder, five (BDNF, TNF-alpha, IL-6, C-reactive protein and cortisol) were the same across the three diagnoses. An analysis of the literature on these molecules showed that, while 65% of studies were cross-sectional and 66% compared biomarker levels between patients and controls in specific disorders, only 10% presented an objective measure of diagnostic or prognostic efficacy. Meta-analyses showed that variation in the levels of these molecules was robust across studies, but also similar among disorders, suggesting them to reflect transdiagnostic systemic consequences of psychiatric illness rather than diagnostic markers. Based on this, we discuss how current publication practices have led to research fragmentation across diagnoses, and what steps can be taken in order to increase clinical translation in the field.

neuroscience↗