Biology subjects

Sachett, A.

Publications and source records attributed to Sachett, A..

9 recordsLinked to original sources

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↗

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↗

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

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↗

bioRxiv2021

Anti-stress effects of the glucagon-like peptide-1 receptor agonist liraglutide in zebrafish

Stress-related disorders are extremely harmful and cause significant impacts on the individual and society. Despite the limited evidence regarding glucagon-like peptide-1 receptor (GLP-1R) and mental disorders, a few clinical and preclinical studies suggest that modulating this system could improve symptoms of stress-related disorders. This study aimed to investigate the effects of liraglutide, a GLP-1R agonist, on neurobehavioral phenotypes and brain oxidative status in adult zebrafish. Acute liraglutide promoted anxiolytic-like effects in the light/dark test, while chronic treatment blocked the impact of unpredictable chronic stress on behavioral and physiological parameters. Taken together, our study demonstrates that liraglutide is active on zebrafish brain and may counteract some of the effects induced by stress. More studies are warranted to further elucidate the potential of GLP-1R agonists for the management of brain disorders.

pharmacology and toxicology↗

bioRxiv2020

How do zebrafish respond to MK-801 and amphetamine? Relevance for assessing schizophrenia-relevant endophenotypes in alternative model organisms

Background and PurposeSchizophrenia pathophysiology has been associated with dopaminergic hyperactivity, loss of parvalbumin-positive GABAergic interneurons, NMDA receptor hypofunction, and redox dysregulation. Most behavioral assays and animal models to study this condition were developed in rodents, leaving room for species-specific biases that could be avoided by cross-species approaches. As MK-801 and amphetamine are largely used in mice and rats to mimic schizophrenia features, this study aimed to investigate the effects of these drugs in zebrafish. Experimental ApproachAdult zebrafish were exposed to MK-801 (1, 5, and 10 M) or amphetamine (0.625, 2.5, and 10 mg{middle dot}L-1) and observed in paradigms of locomotor activity and social behavior. Oxidative parameters relevant to schizophrenia were quantified in brain tissue. Key ResultsMK-801 disrupted social interaction, an effect that resembles the negative symptoms of schizophrenia. It also altered locomotion in a context-dependent manner, with hyperactivity when fish were tested in the presence of social cues and hypoactivity when tested alone. On the other hand, exposure to amphetamine was devoid of effects on locomotion and social behavior, while increased lipid peroxidation in the brain. Conclusion and ImplicationsKey outcomes induced by MK-801 in rodents were replicated in zebrafish, which suggests this species is suitable as an alternative model animal to study psychotic disorders. More studies are necessary to further develop preclinical paradigms with this species and ultimately optimize the screening of potential novel treatments.

neuroscience↗