Biology subjects

Piato, A.

Publications and source records attributed to Piato, A..

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↗

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

3-Nitropropionic acid induces histological and behavioral alterations in adult zebrafish: role of antioxidants on behavioral dysfunction

Huntingtons disease (HD) is a neurodegenerative disease marked by progressive motor and non-motor symptoms such as neuropsychiatric disruption and cognitive dysfunction. It has been reported that some pathogenic mechanisms resulting in neuronal cell death in this disease involve neurodegeneration and oxidative stress. 3-Nitropropionic acid (3-NPA), a natural toxin that promotes the irreversible suppression of mitochondrial complex II, has been used to understand the HD pathogenesis. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral and behavioral phenotype alterations observed in HD. Here we investigated 3-NPA (60 mg/kg) effects on histological and oxidative stress parameters on brain and muscular tissues. We also evaluated the effects of three antioxidant compounds on 3-NPA-induced behavioral phenotypes in adult zebrafish. For the evaluation of the antioxidant effects, adult zebrafish were submitted to a single acute intraperitoneal injection of vitamin C, creatine, or melatonin following 3-NPA chronic administration (60 mg/kg). 3-NPA treatment caused neurodegeneration, but did not alter the muscular tissue. 3-NPA neither change thiobarbituric acid reactive substances (TBARS) nor nonprotein thiol levels. Vitamin C and creatine treatments recovered the hypolocomotion induced by 3-NPA. Also, vitamin C and melatonin treatments improved the memory dysfunction caused by 3-NPA. Altogether, our findings showed that the 3-NPA induces neurodegeneration in adult zebrafish, and the vitamin C, creatine, and melatonin are beneficial in managing HD-like behavioral phenotypes. Thus, these antioxidants could be thought as complementary pharmacotherapies for the treatment of late-stage HD symptoms.

pharmacology and toxicology↗

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↗

bioRxiv2024

Exposure to epoxiconazole induces hyperlocomotion in adult zebrafish

Global agricultural production is sustained by an elevated use of pesticides. Their application in crops results in environmental contamination, which is demonstrated by widespread detections of these chemicals in aquatic ecosystems. This presence poses a risk to non-target organisms and ecological balance since the effects of potential exposure are misunderstood. Epoxiconazole (EPX) is a widely employed triazole fungicide, which has been frequently reported as a contaminant in superficial waters. However, the behavioral effects of EPX exposure in non-target organisms such as fish remain unexplored. We aimed to investigate the effects of EPX exposure on behavioral and biochemical outcomes, using zebrafish as a model organism. For this purpose, a static system was set with concentrations (24, 144, 240 g/L) based on the fungicide environmental detection. The novel tank test (NTT) was performed after 96 h of exposure. The social preference test (SPT) was executed after 120 h, as well as the biochemical assays. In the NTT, the animals increased distance traveled, crossings, entries in the top area, and mean speed, indicating hyperlocomotion. No significant effects were observed in the SPT and the biochemical analyses. We suggest that the increased locomotion is related to the stimulant properties of EPX. Our results contribute to an in-depth understanding of this fungicide effects in zebrafish, which is essential for environmental contamination monitoring and management.

neuroscience↗

bioRxiv2023

Status epilepticus during neurodevelopment increases seizure susceptibility: a model study in zebrafish (Danio rerio)

Epilepsy is among the most common neurological diseases, affecting more than 50 million people worldwide. Unfortunately, one-third of people with epilepsy fail to respond to any current treatment and present a decreased quality of life. Nevertheless, different studies suggest that epilepsies acquired from an initial insult as status epilepticus (SE) followed by epileptogenesis can be prevented. Therefore, it is necessary to establish animal models of epileptogenesis induced by SE. Thus, here we proposed an animal model of epileptogenesis triggered by SE that occurred during the neurodevelopment of zebrafish (Danio rerio). Zebrafish larvae at the 7th day post-fertilization (dpf) were randomly assigned to two experimental groups. One group was exposed to embryo medium. The other group was exposed to pentylenetetrazol (15 mM PTZ) to induce SE. At the 8th dpf, each larva was subjected to the open tank test (OTT) to analyze locomotion and behavioral parameters. After the OTT, each initial group was divided into two groups: animals maintained in embryo medium and animals exposed to PTZ (3 mM), and the susceptibility to PTZ-induced seizure-like behavior was analyzed. Data showed that animals submitted to SE on the 7th dpf showed altered locomotion and behavior 24 hours later. Interestingly, zebrafish larvae submitted to SE on the 7th dpf showed decreased latency to reach seizure-like behavioral stages when exposed to a low concentration of PTZ on the 8th dpf. Concluding, our results show that SE during neurodevelopment increases the susceptibility of zebrafish larvae to present PTZ-induced seizure-like behavior. Our study contributes to the establishment of a model of epileptogenesis in developing zebrafish. Finally, the next step is to improve this model by characterizing molecular, biochemical and physiological markers.

neuroscience↗

bioRxiv2023

N-acetylcysteine and acetyl-L-carnitine did not prevent acute PTZ-induced seizure in adult and larvae zebrafish

Epilepsy is a prevalent neurological disorder, affecting approximately 1 to 2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to the current available pharmacological treatments. Consequently, it is crucial to explore alternative therapeutic options for managing these seizures. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of the neurotransmitter glutamate. Therefore, this study aims to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish, in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances. However, our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and an increase in latencies to higher scores of epileptic seizures. Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.

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↗

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↗

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

Ochratoxin A induces behavioral and neurochemical changes in adult zebrafish

Ochratoxin A (OTA) is a mycotoxin produced by species of filamentous fungi widely found as a contaminant in food and with high toxic potential. Studies have shown that this toxin cause kidney and liver damage, however, data on the effects of exposure to OTA on the central nervous system are still scarce. Zebrafish (Danio rerio) is a teleost often used in translational research due to its physiological, genetic, and behavioral homology with mammals, in addition to being useful as an environmental bioindicator. Thus, this study aimed to investigate the effects of exposure to OTA on behavioral and neurochemical parameters in adult zebrafish. The animals were treated with different doses of OTA (1.38, 2.77, and 5.53 mg/kg) and submitted to behavioral evaluations in the open tank and social interaction tests. Subsequently, they were euthanized, and the brains were used to assess markers associated with oxidative status. In the open tank test OTA induced changes in distance, absolute turn angle, mean speed, and time-freezing. However, no significant effects were observed in the social interaction test. Moreover, OTA also induced alterations in neurochemical parameters with changes in non-protein thiols (NPSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). This study showed that OTA can affect neurobiological aspects in zebrafish even at low doses.

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↗