Abstract Chronic stress may cause physical, behavioral and neuropsychiatric changes, affecting the health condition of an individual. Aggression is a universal behavior with great relevance on human ...and animal social systems. Despite studies showing the influence of chronic stress on aggression, the effects of unpredictable chronic stress (UCS) on aggressive behavior in male and female zebrafish remain unknown. Thus, the aim of this study was to evaluate the effects of UCS on the aggressive behavior and cortisol levels in adult zebrafish of both sexes. Our results showed that UCS increased aggression in males, but not in females, which displayed more aggressive behavior at baseline than control males. Increased whole-body cortisol levels were observed in stressed males; however, no differences were found between female groups. In conclusion, we reported for the first time gender differences on behavioral parameters and cortisol levels in response to UCS in zebrafish. These results highlight the relevance of studying behavioral and physiological parameters in both sexes separately.
Schizophrenia pathophysiology is associated with hypofunction of glutamate NMDAreceptors (NMDAR) in GABAergic interneurons and dopaminergic hyperactivation in subcorticalbrain areas. The ...administration of NMDAR antagonists is used as an animal model that replicatesbehavioral phenotypes relevant to the positive, negative, and cognitive symptoms of schizophrenia.Such models overwhelmingly rely on rodents, which may lead to species-specific biases and poortranslatability. Zebrafish, however, is increasingly used as a model organism to study evolutionarilyconserved aspects of behavior. We thus aimed to review and integrate the major findings reportedin the zebrafish literature regarding the behavioral effects of NMDAR antagonists with relevance toschizophrenia. We identified 44 research articles that met our inclusion criteria from 590 studiesretrieved from MEDLINE (PubMed) and Web of Science databases. Dizocilpine (MK-801) andketamine were employed in 29 and 10 studies, respectively. The use of other NMDAR antagonists,such as phencyclidine (PCP), APV, memantine, and tiletamine, was described in 6 studies. Frequentlyreported findings are the social interaction and memory deficits induced by MK-801 andcircling behavior induced by ketamine. However, mixed results were described for several locomotorand exploratory parameters in the novel tank and open tank tests. The present review integratesthe most relevant results while discussing variation in experimental design and methodologicalprocedures. We conclude that zebrafish is a suitable model organism to study drug-induced behavioralphenotypes relevant to schizophrenia. However, more studies are necessary to further characterizethe major differences in behavior as compared to mammals.
Pesticide commercial mixtures, including the insecticide fipronil and the fungicides pyraclostrobin and methyl-thiophanate, have been used in concomitant pest control, facilitating agricultural ...management. Their widespread use can lead to soil and water contamination and potentially induce damages in the ecosystem, producing toxic effects in non-target organisms. Despite their toxicological potential, their effects on behavioral and biochemical parameters are not well understood. Here we investigated the effects of the mixture of fipronil and fungicides (MFF) pyraclostrobin and methyl- thiophanate on behavioral and biochemical parameters of oxidative stress in adult zebrafish. Animals exposed to the highest MFF tested concentration showed a decrease in the total distance traveled and in the number of crossings in the different zones of the tank. Furthermore, animals exposed to highest MFF tested concentration spent more time in water surface. In addition, our data showed that the exposure to this preparation promoted a decrease in non-protein thiol content as well as in catalase activity. Finally, pesticide exposure induced an increase in the superoxide dismutase/catalase ratio. Our results indicate that alterations in behavioral and oxidative parameters are involved in MFF toxicity in zebrafish. The antioxidant mechanisms analyzed were altered in concentrations that did not affect zebrafish behavior. Therefore, the assessment of oxidative stress parameters in zebrafish brains could be very useful to detect the early effects of environmental exposure to the MFF.
Anxiety disorders are highly prevalent and a leading cause of disability worldwide. Their etiology is related to stress, an adaptive response of the organism to restore homeostasis, in which ...oxidative stress and glutamatergic hyperactivity are involved.
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-Acetylcysteine (NAC) is a multitarget approved drug proved to be beneficial in the treatment of various mental disorders. Nevertheless, NAC has low membrane permeability and poor bioavailability and its limited delivery to the brain may explain inconsistencies in the literature.
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-Acetylcysteine amide (AD4) is a synthetic derivative of NAC in which the carboxyl group was modified to an amide. The amidation of AD4 improved lipophilicity and blood-brain barrier permeability and enhanced its antioxidant properties. The purpose of this study was to investigate the effects of AD4 on behavioral and biochemical parameters in zebrafish anxiety models. Neither AD4 nor NAC induced effects on locomotion and anxiety-related parameters in the novel tank test. However, in the light/dark test, AD4 (0.001 mg/L) increased the time spent in the lit side in a concentration 100 times lower than NAC (0.1 mg/L). In the acute restraint stress protocol, NAC and AD4 (0.001 mg/L) showed anxiolytic properties without meaningful effects on oxidative status. The study suggests that AD4 has anxiolytic effects in zebrafish with higher potency than the parent compound. Additional studies are warranted to characterize the anxiolytic profile of AD4 and its potential in the management of anxiety disorders.
The enriched environment (EE) is a laboratory housing model that emerged from efforts to minimize the impact of environmental conditions on laboratory animals. Recently, we showed that EE promoted ...positive effects on behavior and cortisol levels in zebrafish submitted to the unpredictable chronic stress (UCS) protocol. Here, we expanded the characterization of the effects of UCS protocol by assessing parameters of oxidative status in the zebrafish brain and reveal that EE protects against the oxidative stress induced by chronic stress.
Zebrafish were exposed to EE (21 or 28 days) or standard housing conditions and subjected to the UCS protocol for seven days. Oxidative stress parameters (lipid peroxidation (TBARS), reactive oxygen species (ROS) levels, non-protein thiol (NPSH) and total thiol (SH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured in brain homogenate.
Our results revealed that UCS increased lipid peroxidation and ROS levels, while decreased NPSH levels and SOD activity, suggesting oxidative damage. EE for 28 days prevented all changes induced by the UCS protocol, and EE for 21 days prevented the alterations on NPSH levels, lipid peroxidation and ROS levels. Both EE for 21 or 28 days increased CAT activity.
Our findings reinforce the idea that EE exerts neuromodulatory effects in the zebrafish brain. EE promoted positive effects as it helped maintain the redox homeostasis, which may reduce the susceptibility to stress and its oxidative impact.
Studies have suggested that oxidative stress may contribute to the pathogenesis of mental disorders. In this context, molecules with antioxidant activity may be promising agents in the treatment of ...these deleterious conditions. Acetyl-L-carnitine (ALC) is a multi-target molecule that modulates the uptake of acetyl-CoA into the mitochondria during fatty acid oxidation, acetylcholine production, protein, and membrane phospholipid synthesis, capable of promoting neurogenesis in case of neuronal death. Moreover, neurochemical effects of ALC include modulation of brain energy and synaptic transmission of multiple neurotransmitters, including expression of type 2 metabotropic glutamate (mGlu2) receptors. The aim of this study was to investigate the effects of ALC in zebrafish by examining behavioral and biochemical parameters relevant to anxiety and mood disorders in zebrafish. ALC presented anxiolytic effects in both novel tank and light/dark tests and prevented the anxiety-like behavior induced by an acute stressor (net chasing). Furthermore, ALC was able to prevent the lipid peroxidation induced by acute stress in the zebrafish brain. The data presented here warrant further investigation of ALC as a potential agent in the treatment of neuropsychiatric disorders. Its good tolerability also subsidizes the additional studies necessary to assess its therapeutic potential in clinical settings.
Chronological aging in later life is associated with brain degeneration processes and increased risk for disease such as stroke and dementia. With a worldwide tendency of aging populations and ...increased longevity, mental health, and psychiatric research have paid increasing attention to understanding brain-related changes of aging. Recent findings suggest there is a
(a difference between chronological age and brain age predicted by brain imaging indices); the magnitude of the gap may indicate early onset of brain aging processes and disease. Artificial intelligence has allowed for a narrowing of the gap in chronological and predicted brain age. However, the factors that drive model predictions of brain age are still unknown, and there is not much about these factors that can be gleaned from the black-box nature of machine learning models. The goal of the present study was to test a brain age regression approach that is more amenable to interpretation by researchers and clinicians.
Using convolutional neural networks we trained multiple regressor models to predict brain age based on single slices of magnetic resonance imaging, which included gray matter- or white matter-segmented inputs. We evaluated the trained models in all brain image slices to generate a final prediction of brain age. Unlike whole-brain approaches to classification, the slice-level predictions allows for the identification of which brain slices and associated regions have the largest difference between chronological and neuroimaging-derived brain age. We also evaluated how model predictions were influenced by slice index and plane, participant age and sex, and MRI data collection site.
The results show, first, that the specific slice used for prediction affects prediction error (i.e., difference between chronological age and neuroimaging-derived brain age); second, the MRI site-stratified separation of training and test sets removed site effects and also minimized sex effects; third, the choice of MRI slice plane influences the overall error of the model.
Compared to whole brain-based predictive models of neuroimaging-derived brain age, slice-based approach improves the interpretability and therefore the reliability of the prediction of brain age using MRI data.
Muscle cramps profile among spinocerebellar ataxias Franklin, Gustavo; Ferreira Camargo, Carlos; Balaban, Daniel ...
Annals of Indian Academy of Neurology,
07/2022, Letnik:
25, Številka:
4
Journal Article
PDF
