Biology subjects

Gallas-Lopes, M.

Publications and source records attributed to Gallas-Lopes, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Unpredictable chronic stress redistributes novelty-evoked exploratory space use and yields method-dependent identification of resilient-like archetypes in zebrafish

Unpredictable chronic stress (UCS) produces heterogeneous behavioural outcomes, but identifying resilient individuals remains challenging because post-stress behaviour is multidimensional and classification depends on the analytical framework. We characterised novelty-evoked exploration in 178 adult zebrafish (89 unstressed reference, 89 UCS-exposed) using four Novel Tank Test variables: distance travelled, line crossings, upper-zone entries and upper-zone time, from a historical LAPCOM dataset from four independent cohorts. Behaviour was robustly normalised to control distributions within cohorts. In the unstressed population, principal component analysis revealed a dominant exploratory gradient (PC1 = 74.9%; PC2 = 18.7%), whereas weighted k-nearest-neighbour Louvain analysis yielded a stable two-profile partition. However, null-model inference and resampling did not support discrete behavioural populations, indicating a predominantly continuous reference architecture. UCS significantly redistributed individuals within this architecture (PERMANOVA: F(1,173) = 8.10, R2= 0.0423, p = 0.0016), reducing occupancy of the higher-exploration reference profile from 55.1% to 24.7%, while multivariate dispersion, Mahalanobis distance and global correlation structure showed no detectable differences. De novo Louvain analysis identified lower- and higher-exploration configurations, but correspondence with the control reference was asymmetric: all 44 lower-exploration fish mapped to the lower reference profile, whereas only 22 of 45 higher-exploration fish mapped to the higher reference profile. Thus, higher exploration after UCS was insufficient to define a resilient-like response. Across five analytical frameworks, resilient assignments ranged from 9 to 45 individuals and susceptible assignments from 23 to 68, with partial individual-level convergence. These findings support reference-integrated behavioural stratification for identifying resilient- and susceptible-like candidates for physiological, cellular and molecular validation.

neuroscience↗

bioRxiv2026

Modulation of social behavior in adult zebrafish (Danio rerio): a systematic review and meta-analysis

Social behavior is a fundamental phenotype across vertebrates. Zebrafish (Danio rerio) have emerged as a valuable translational model for investigating the neurobiological mechanisms underlying sociability, particularly due to their robust shoaling behavior and experimental tractability. However, the literature presents issues of reproducibility and inconsistent findings regarding the modulation of social preference and shoal cohesion in adult zebrafish. We conducted a systematic review and meta-analysis to synthesize studies evaluating the effects of pharmacological interventions that modulate the central nervous system and stress-related interventions on social behavior in adult zebrafish and, when available, anxiety-like behavior. The literature search was performed in three databases (Embase, PubMed, and Web of Science), followed by a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Interventions from the included studies (n = 108) were categorized according to their nature, mechanism of action, and/or therapeutic purpose, resulting in seven, four, and five meta-analyses for social preference, shoal cohesion, and anxiety-related tests, respectively. Ethanol, NMDA antagonists, pro-dopaminergic agents, and stress-related interventions decreased social preference, while stress-related interventions increased shoal cohesion. The fact that stress produced opposite effects suggests that these paradigms measure distinct sociability constructs, or perhaps are differentially modulated by confounding factors, like anxiety for example. The studies presented high heterogeneity, with prediction intervals compatible with effects in both directions, as well as methodological limitations and deficiencies in data reporting, as evidenced by the risk of bias assessment. These findings emphasize the need for well-designed new studies to validate the findings and expand the evidence on interventions that currently lack sufficient studies for quantitative synthesis.

neuroscience↗

bioRxiv2026

Effects of NMDA antagonists on social behaviour: a systematic review and meta-analysis of preclinical studies

Social withdrawal is a key component of the negative symptom domain of schizophrenia, and pharmacological blockade of the N-methyl-D-aspartate receptor (NMDAR) is widely used to model schizophrenia-relevant phenotypes in animals. However, findings on social behaviour are inconsistent across paradigms and laboratories. We therefore conducted a systematic review and meta-analysis to synthesise the effects of dizocilpine, ketamine, and phencyclidine on social interaction and social preference, to evaluate whether clinically approved antipsychotics modify these outcomes, and to examine locomotor activity measured within the same social tests to aid interpretation. We searched Embase, PubMed and Web of Science without language or date restrictions. Controlled in vivo studies in laboratory animals administering an eligible NMDAR antagonist and reporting social interaction and/or social preference outcomes were included. Two reviewers independently screened records, extracted data and assessed risk of bias. Effect sizes were computed as standardised mean differences and synthesised using correlated multilevel random-effects models with cluster-robust variance estimation. In total, 264 studies met the inclusion criteria. Overall, NMDAR antagonists were associated with reduced social interaction and reduced social preference relative to controls, although the social preference literature appeared vulnerable to small-study effects and imprecision. Locomotor activity measured during social interaction tests tended to be higher following NMDAR antagonists, whereas during social preference no consistent overall change was observed. In animals exposed to NMDAR antagonists, antipsychotics increased social behaviour, but these changes commonly co-occurred with reduced locomotion during social interaction tests, suggesting that improvements in social measures may partly reflect altered behavioural competition and time allocation rather than selective restoration of social functioning. Taken together, the evidence supports an overall link between NMDAR antagonism and reduced social behaviour, but the strength and interpretability of this signal depend on the paradigm and are constrained by heterogeneity and limitations in reporting.

pharmacology and toxicology↗

bioRxiv2025

Unpredictable chronic stress does not alter social behavior in zebrafish

Stress-related disorders encompass diverse behavioral alterations, including impaired social functioning. The zebrafish (Danio rerio) is a valuable model for studying these phenomena, particularly because of its robust and ethologically conserved social behaviors. Unpredictable chronic stress (UCS) produces behavioral, physiological, and molecular changes in zebrafish that parallel core features of human anxiety and depressive disorders; however, its impact on social outcomes remains unclear. Here, we examined whether a 14-day UCS protocol alters social behavior in adult zebrafish using two complementary assays: the social preference test and the shoal cohesion test. Across two independent experiments, UCS did not elicit detectable changes in individual social approach or group-level cohesion. In contrast, UCS induced clear anxiety-like behavior in the novel tank test, validating the stress manipulation, with stressed fish displaying reduced vertical exploration and decreased time in the upper zone. Shoal cohesion measures showed a time-dependent decrease in both groups, consistent with habituation to the testing environment rather than a stress-specific effect. Together, these results suggest that social behavior in adult zebrafish is relatively resilient to UCS under the conditions tested, whereas anxiety-like responses are markedly affected. Future work should investigate whether factors such as stressor intensity, developmental stage, sex composition, or social hierarchy modulate the sensitivity of social behavior to chronic stress.

neuroscience↗

bioRxiv2025

Ketamine-induced NMDA receptor hypofunction alters social and locomotor behavior in adult zebrafish

BackgroundNMDA receptor antagonists, such as ketamine, are widely used to model schizophrenia-related phenotypes in preclinical studies. While zebrafish have emerged as a promising model organism for neuropsychiatric research, few studies have characterized their behavioral responses to repeated ketamine exposure. MethodsThree independent experiments were conducted to evaluate the acute, repeated and sustained behavioral effects of ketamine in adult zebrafish. In Experiment I, fish were exposed to 10, 20, or 40 mg/L ketamine once daily for five days, and submitted to the social preference (SPT) and open tank (OTT) tests on days 1 and 5, and re-exposed and re-tested on day 7 after a 48-hour washout. Experiments II and III assessed whether behavioral changes persisted following 5- or 14-day exposure protocols, with testing conducted 48 hours after the final treatment. ResultsKetamine induced robust, concentration-dependent alterations in Experiment I: it reduced social interaction and increased locomotor activity in the SPT on all experimental days, while increased rotational behavior in the OTT on days 1 and 5. These effects did not intensify over repeated exposure and were not sustained after a 48-hour washout in either protocol (Experiments II and III). ConclusionsThe results support the utility of zebrafish for modeling acute behavioral responses to NMDA receptor antagonism, capturing features of schizophrenia-like phenotypes. However, no evidence of behavioral sensitization or lasting disruption was observed, diverging from rodent studies. Future studies should incorporate antipsychotic validation, neurochemical analyses, and alternative exposure strategies to further develop zebrafish as a translational model for psychiatric research.

pharmacology and toxicology↗

bioRxiv2025

Neurological effects induced by micro- and nanoplastics in fish: a systematic review and meta-analysis

Plastic is considered an inert material with high durability and minimal to virtually no decomposition. However, when released into the environment, they can degrade into very small particles, forming micro- and nanoplastic particles (MNP). This systematic review and meta-analysis synthesized the evidence from controlled preclinical studies to investigate the neurological effects of MNPs in fish. Following a pre-registered protocol, we searched PubMed, Web of Science, and Scopus for studies exposing fish to virgin MNPs under controlled conditions, reporting behavioral or neurochemical outcomes relevant to central nervous system function. Data were synthesized using a hierarchical random-effects model with robust variance estimation. Fifty-nine studies, comprising 723 comparisons across 13 behavioral and neurochemical outcomes, were included in the meta-analysis. The analysis accounted for correlated effect sizes within shared control groups; and nested identifiers for study, control group, and effect size. Results indicated high heterogeneity and no consistent effect of the MNP exposure on behavioral or neurochemical parameters, except for reduced traveled distance in sensory-motor assays. Meta-regression examined whether developmental stage, exposure duration, and MNP size or concentration moderate these effects. No significant moderators were identified, except for catalase activity, where longer exposure reduced enzyme activity in larvae. The findings should be interpreted with caution, as reporting quality was generally low, with key methodological details often omitted. Additionally, publication bias was found for several outcomes, and influential case analyses revealed that a few studies disproportionately affected the overall estimates. Further studies are needed to clarify the impact of MNPs on fish neurobiology and behavior.

neuroscience↗

bioRxiv2025

Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish

BackgroundLinalool (LIN) and trans-nerolidol (NER) are terpene alcohols found in plant-derived essential oils commonly used in traditional systems of medicine. Both compounds have shown antiseizure, sedative, and antioxidant effects in rodent and in vitro models. Due to their structural similarity, a comparative evaluation of their antiseizure profiles is warranted. This study examined the effects of acute LIN and NER exposure in a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio). MethodsA total of 240 adult zebrafish were randomly assigned to the following groups: blank control (dechlorinated water), vehicle control (1% DMSO), positive control (50 {micro}M diazepam, DZP), and three concentrations of LIN or NER (4, 40, 400 {micro}M). Fish were exposed to treatments for 10 minutes, transferred to a washout beaker with dechlorinated water for 5 minutes, and then transferred to PTZ (10 mM) for 20-minute behavioral recording. Seizure activity was scored by blinded observers (BORIS(R)), and locomotion was analyzed with ANY-maze software. ResultsLIN at 400 {micro}M and NER at 40 and 400 {micro}M significantly prolonged latency to clonic- and tonic-like seizures and reduced seizure severity. Notably, 400 {micro}M NER exceeded DZP in effect size, and 40 {micro}M NER also enhanced locomotor activity. ConclusionLIN and NER delayed progression to severe seizure stages and reduced seizure severity, supporting their antiseizure potential. NER consistently outperformed LIN, demonstrating stronger efficacy than DZP at the highest concentration. Consistent with rodent studies, these findings position both as promising leads for drug development.

neuroscience↗

bioRxiv2024

EPILEPTOGENESIS INHIBITS THE CIRCADIAN CLOCK AND RESHAPES THE DIURNAL TRANSCRIPTOMIC RHYTHMICITY IN THE MOUSE HIPPOCAMPUS

Epileptogenesis is the process that leads the brain into epileptic activity. Clinical evidence shows that [~]90% of people with epilepsy present rhythmicity in the timing of their seizures presentation. However, whether the circadian clock is a key player during epileptogenesis remains unknown. Here, we triggered epileptogenesis in mice by the intra-amygdala injection of kainic acid and profiled by RNA sequencing their hippocampal diurnal mRNA rhythmicity. We show that epileptogenesis largely reshapes the hippocampal transcriptomic rhythmicity and that the molecular clock machinery is inhibited due to the disruption of the core clock gene Bmal1. We identified relevant dysregulated pathways and their dynamics in epileptogenesis, predicting a key role for microglial-driven neuroinflammation. We predicted the genes that Bmal1 is directly controlling over time. Finally, we sought for translational relevance evidence by performing RNA sequencing in hippocampal samples resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and cross-analyzing datasets.

neuroscience↗

bioRxiv2024

Evaluation of behavioral and neurochemical changes induced by carbofuran in zebrafish (Danio rerio)

Carbofuran (CF) is a carbamate class pesticide, widely used in agriculture for pest control in crops. On the other hand, CF is also detected as a contaminant in food and water sources. This pesticide has high toxicity in non-target organisms, and its presence in the environment poses a threat to the ecosystem. Research has revealed that this pesticide acts as an inhibitor of acetylcholinesterase (AChE), inducing an accumulation of acetylcholine in the brain. Consequently, this leads to the emergence of a cholinergic syndrome and various detrimental effects on human health. Nonetheless, our understanding of CF impact on the central nervous system remains elusive. Therefore, this study aimed to investigate the effects of CF on behavioral and neurochemical parameters in adult zebrafish. The animals were exposed for 96 hours to different concentrations of CF (5, 50, and 500 {micro}g/L) and subjected to behavioral assessments in the novel tank test (NTT) and social preference test (SPT). Subsequently, they were euthanized, and their brains were used to evaluate neurochemical markers associated with oxidative stress and AChE levels. In the NTT and SPT, CF did not alter the evaluated behavioral parameters. Furthermore, CF did not affect the levels of AChE, non-protein sulfhydryl groups, and thiobarbituric acid reactive species in the zebrafish brain. However, further research is needed regarding the environmental exposure of this compound to non-target organisms.

neuroscience↗

bioRxiv2023

Chemically-induced epileptic seizures in zebrafish: a systematic review

The use of zebrafish as a model organism is gaining evidence in the field of epilepsy as it may help to understand the mechanisms underlying epileptic seizures. As zebrafish assays became popular, the heterogeneity between protocols increased, making it hard to choose a standard protocol to conduct research while also impairing the comparison of results between studies. We conducted a systematic review to comprehensively profile the chemically-induced seizure models in zebrafish. Literature searches were performed in PubMed, Scopus and Web of Science, followed by a two-step screening process based on inclusion/exclusion criteria. Qualitative data were extracted and a sample of 100 studies was randomly selected for risk of bias assessment. Out of the 1058 studies identified after removing duplicates, 201 met the inclusion criteria. We found that the most common chemoconvulsants used in the reviewed studies were pentylenetetrazole (n = 180), kainic acid (n = 11), and pilocarpine (n = 10), which increase seizure severity in a dose-dependent manner. The main outcomes assessed were seizure scores and locomotion. Significant variability between the protocols was observed for administration route, duration of exposure, and dose/concentration. Of the studies subjected to risk of bias assessment, most were rated as low risk of bias for selective reporting (94%), baseline characteristics of the animals (67%), and blinded outcome assessment (54%). Randomization procedures and incomplete data were rated as unclear in 81% and 68% of the studies, respectively. None of the studies reported the sample size calculation. Overall, these findings underscore the need for improved methodological and reporting practices to enhance reproducibility and reliability of zebrafish models for studying epilepsy. Our study offers a comprehensive overview of the current state of chemically-induced seizure models in zebrafish, highlighting the common chemoconvulsants used and the variability in protocol parameters. This may be particularly valuable to researchers interested in understanding the underlying mechanisms of epileptic seizures and screening potential drug candidates in zebrafish models. HIGHLIGHTS- We systematically reviewed the effects of chemically-induced seizures in zebrafish; - PTZ is the most used epileptic seizure inducer in zebrafish; - More than 50% of the studies fail to report data such as outlier exclusion criteria and sample size estimation; - The results showed a need for better standardization of protocols.

neuroscience↗

bioRxiv2023

Neurobehavioral effects of fungicides in zebrafish: a systematic review and meta-analysis

With the aim of yielding high productivity levels, pesticides are widely used in global agriculture. Among them, fungicides are compounds intended to inhibit fungal proliferation in crops and seeds. Their application often leads to environmental contamination, with these chemicals persistently being detected in surface waters. This presence may threaten non-target organisms that dwell in the affected ecosystems, including humans. In toxicologic research, the zebrafish (Danio rerio) is the most used fish species to assess the potential effects of fungicide exposure, generating numerous and sometimes conflicting findings. We conducted a systematic review and meta-analysis aiming to synthesize the neurobehavioral effects of fungicides in zebrafish. The search was performed in three databases (PubMed, Scopus, and Web of Science) and the screening was based on a two-stage process guided by pre-defined inclusion/exclusion criteria. Qualitative and quantitative data, as well as reporting quality, were extracted from the included studies (n = 60). Meta-analyses were performed for the outcomes of distance traveled in larvae and adults, and spontaneous movements in embryos. We found an overall significant effect of fungicide exposure on distance, which was lower in exposed versus control groups (SMD -0.44 [-0.74; -0.13], p = 0.0055). No effect was observed for spontaneous movements. The overall heterogeneity for distance and spontaneous movements was considered high (I2 = 80%) and moderate (I2 = 74%), respectively. This can be explained by substantial methodological variation between protocols, whereas a poor reporting practice hinders the proper critical evaluation of the findings. However, a sensitivity analysis did not indicate any study skewing the meta-analyses. This review demonstrates the need for better-designed and reported experiments in this field. Highlights- We systematically reviewed the behavioral effects of fungicides in zebrafish - Fungicides decrease the distance traveled - Fungicide exposure has no significant effects on spontaneous movements - Moderate to high levels of heterogeneity were found - The results showed a need for better-designed studies with clarity of report

pharmacology and toxicology↗

bioRxiv2023

Is environmental enrichment beneficial for laboratory animals? A systematic review of studies in zebrafish

Environmental enrichment (EE) consists of a series of interventions that are carried out in the home environment to provide greater exposure to sensory stimuli with the objective of mimicking the natural habitat for the animals housed in the laboratory, offering a more complex environment like those found in nature. Some studies have shown the positive effects of EE on zebrafish housed in a laboratory environment. However, this evidence is still very recent and accompanied by contradictory results. Furthermore, there is great variability in the protocols applied, and in the conditions of the tests, tanks, and materials used for creating an EE environment. This substantial variability can bring many uncertainties to the development of future studies and hinder the reproducibility and replicability of research. In this context, the main objective of this study was to carry out a systematic review of the literature aiming to provide an overview of the EE protocols used in zebrafish. We conducted a systematic review following PRISMA recommendations. The literature search was performed in PubMed, Scopus, and Web of Science databases and the studies were selected based on inclusion/exclusion criteria. We performed data extraction and risk of bias analysis of the studies included. A total of 901 articles were identified in the databases and 27 of these studies were included in this review. Among these studies, the effect of EE was evaluated as two different proposals. (1) to improve animal welfare and (2) as an intervention for the prevention of some disorders. Although the zebrafish EE protocols presented a series of experimental differences, the results showed that the benefits of the EE for zebrafish were robust. According to the results described here, the use of EE in the zebrafish home tank provides better welfare and may reduce sources of bias in scientific experiments, such as high-stress levels and fighting events.

animal behavior and cognition↗

bioRxiv2022

Ten years of unpredictable chronic stress in zebrafish: a systematic review and meta-analysis

The zebrafish (Danio rerio) is a model animal that is being increasingly used in neuroscience research. A decade ago, the first study on unpredictable chronic stress (UCS) in zebrafish was published, inspired by protocols established for rodents in the early 1980s. Since then, several studies have been published by different groups, in some cases with conflicting results. We conducted a systematic review to identify studies evaluating the effects of UCS in zebrafish and meta-analytically synthetized the data of neurobehavioral outcomes and relevant biomarkers. Literature searches were performed in three databases (PubMed, Scopus, and Web of Science) and a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Outcomes of included studies (n = 38) were grouped into anxiety/fear- related behaviour, locomotor function, social behaviour, or cortisol level domains. UCS increased anxiety/fear-related behaviour and cortisol levels while decreased locomotor function, but a significant summary effect was not observed for social behaviour. Despite including a significant number of studies, the high heterogeneity and the methodological and reporting problems evidenced in the risk of bias analysis make it difficult to assess the internal validity of most studies and the overall validity of the model. Our review thus evidences the need to conduct well-designed experiments to better evaluate the effects of UCS on the behaviour of zebrafish.

neuroscience↗

bioRxiv2022

Effects of taurine in mice and zebrafish behavioral assays with translational relevance to schizophrenia

BackgroundAltered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate NMDA receptor antagonist. MethodsC57BL/6 mice were intraperitoneally administered with saline or taurine (50, 100 and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150 and 400 mg/L) followed by MK-801 (5 M); social interaction and locomotor activity were evaluated in the same test. ResultsMK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability while increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. DiscussionContradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models of relevance to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.

pharmacology and toxicology↗

bioRxiv2021

What do zebrafish prefer? Directional and color preferences in maze tasks

Studies regarding the animals innate preferences help elucidate and avoid probable sources of bias and serve as a reference to improve and develop new behavioral tasks. In zebrafish research, the results of innate directional and color preferences are often not replicated between research groups or even inside the same laboratory raising huge concerns on the replicability and reproducibility. Thus, this study aimed to investigate the male and female zebrafish innate directional and color preferences in the plus-maze and T-maze behavioral tasks. As revealed by the percentage of time spent in each zone of the maze, our results showed that males and females zebrafish demonstrated no difference in directional preference in the plus-maze task. Surprisingly, male and female zebrafish showed color preference differences in the plus-maze task; males did not show any color preference, while female zebrafish demonstrated a red preference compared to white, blue, and yellow colors. Moreover, both male and female zebrafish demonstrated a strong black color preference compared to the white color in the T-maze task. Thus, our results demonstrate the importance of innate preference assays involved with the directionality of the apparatus or the application of colors as a screening process conducting behavioral tests (e.g., anxiety, learning and memory assessment, locomotion, and preference) and highlight the need to analyze sex differences.

neuroscience↗

bioRxiv2021

Micronized curcumin causes hyperlocomotion in zebrafish larvae

Zebrafish larvae have been widely used in neuroscience and drug research and development. In the larval stage, zebrafish present a broad behavioral repertoire and physiological responses similar to adults. Curcumin (CUR), a major component of Curcuma longa L. (Zingiberaceae), has demonstrated the ability to modulate several neurobiological processes relevant to mental disorders in animal models. However, the low bioavailability of this compound can compromise its in vivo biological potential. Interestingly, it has been shown that micronization can increase the biological effects of several compounds. Thus, in this study, we compared the effects of acute exposure for 30 minutes to the following solutions: water (control), 0.1% DMSO (vehicle), 1 M CUR, or 1 M micronized curcumin (MC) in zebrafish larvae 7 days post-fertilization (dpf). We analyzed locomotor activity (open tank test), anxiety (light/dark test), and avoidance behavior (aversive stimulus test). Moreover, we evaluated parameters of oxidative status (thiobarbituric acid reactive substances and non-protein thiols levels). MC increased the total distance traveled and absolute turn angle in the open tank test. There were no significant differences in the other behavioral or neurochemical outcomes. The increase in locomotion induced by MC may be associated with a stimulant effect on the central nervous system, which was evidenced by the micronization process.

neuroscience↗

bioRxiv2021

Non-micronized and micronized curcumin do not prevent the behavioral and neurochemical effects induced by acute stress in zebrafish

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), presents neuroprotective properties and can modulate neuronal pathways related to mental disorders. However, curcumin has low bioavailability, which can compromise its use. The micronization process can reduce the mean particle diameter and improve this compounds bioavailability and therapeutic potential. In this study, we compared the behavioral (in the open tank test, OTT) and neurochemical (thiobarbituric acid reactive substances (TBARS) and non-protein thiols (NPSH) levels) effects of non-micronized curcumin (CUR, 10 mg/kg, i.p.) and micronized curcumin (MC, 10 mg/kg, i.p.) in adult zebrafish subjected to 90-minute acute restraint stress (ARS). ARS increased the time spent in the central area and the number of crossings and decreased the immobility time of the animals. These results suggest an increase in locomotor activity and a decrease in thigmotaxis behavior in the OTT. Furthermore, ARS also induced oxidative damage by increasing TBARS and decreasing NPSH levels. ARS-induced behavioral and biochemical effects were not blocked by any curcumin preparation. Therefore, we suppose that curcumin does not have anti-stress effects on the ARS in zebrafish.

neuroscience↗

bioRxiv2021

Curcumin micronization by supercritical fluid: in vitro and in vivo biological relevance

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared the in vitro antioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC (1 g/L) presented higher antioxidant activity in vitro as compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2-2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CUR in vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity both in vitro and in vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.

neuroscience↗