A new approach to explore the correlation between declarative memory and anxiety in animal models of schizophrenia and microplastic pollution.

The discovery of new detrimental effects associated with microplastic pollution is ever-growing and reaching alarming rates worldwide, as it is linked to numerous disorders such as lung diseases, gastrointestinal problems, and cancer. However, a less explored issue is their impact on mental health, more precisely schizophrenia, even though several studies have shown the presence of microplastics in air, water, soil, and even food, thus making them a significant part of our daily dietary intake. It is also well known that declarative memory and anxiety levels are impaired in schizophrenia. However, apart from the novel object recognition test, the possibilities for testing memory in zebrafish are quite limited. For these reasons, we designed a novel memory test based on rewards, a learning period, and zebrafish's natural preference for certain colors. Among the results, our fish preferred the color yellow over red, and we illustrated that ketamine and its combination with methionine provide a robust model that seems to better represent the aspects of schizophrenia in animal models. Moreover, surprisingly, we observed that microplastics (more precisely, polypropylene fibers) ingested by animals through the diet seem to act as a buffer against ketamine toxicity and as an enhancer for methionine exposure. Moreover, according to our results, groups with higher anxiety levels seem to perform better on the memory test.

Histopathological and Behavioral Impairments in Zebrafish (Danio rerio) Chronically Exposed to a Cocktail of Fipronil and Pyriproxyfen.

BACKGROUND: Lately, the high incidence of pesticide usage has attracted everyone's interest due to the serious effects produced. Fipronil (FIP) is a phenylpyrazole compound that acts on the insect's GABA neurotransmitter by inhibiting its activity. Moreover, the literature reports highlight its implication in neurodevelopmental abnormalities and oxidative stress production in different organisms. Similarly, pyriproxyfen (PYR) is known to affect insect activity by mimicking the natural hormones involved in the maturation of the young insects. The aim of the present study was to investigate the impact of the mixture of these pesticides on the tissues and behavior of zebrafish. METHODS: To assess the influence of this cocktail on zebrafish, three groups of animals were randomly selected and exposed to 0, 0.05, and 0.1 mg L-1 FIP and PYR mixture for five days. The fish were evaluated daily by the T-maze tests for locomotor activity and the light-dark test and recordings lasted four min. The data were quantified using the EthoVision software. RESULTS: Our results indicated significant changes in locomotor activity parameters that showed increased levels following exposure to the mixture of FIP and PYR. On the other hand, the mixture also triggered anxiety in the zebrafish, which spent more time in the light area than in the dark area. In addition, mixture-induced histological changes were observed in the form of numerous hemosiderin deposits found in various zebrafish tissues. CONCLUSIONS: The current findings indicate that the mixture of FIP and PYR can have considerable consequences on adult zebrafish and may promote or cause functional neurological changes in addition to histological ones.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

Vitamin C Attenuates Oxidative Stress and Behavioral Abnormalities Triggered by Fipronil and Pyriproxyfen Insecticide Chronic Exposure on Zebrafish Juvenile.

Chronic exposure to synthetic insecticides in the early life of a child can lead to a series of disorders. Several causes as parental age, maternal smoking, birth complications, and exposure to toxins such as insecticides on childhood can lead to Autism spectrum disorder (ASD) occurrence. The aim of this study was to evaluate the potential protective role of vitamin C (Vit. C) from children's supplements after 14 days chronic exposure to insecticide mixture fipronil (Fip) + pyriproxyfen (Pyr) on juvenile zebrafish for swimming performances, social behavior and oxidative stress associated with ASD model. Juvenile (14-17 mm) wild-type AB zebrafish (Danio rerio) (45 days) were exposed to relevant concentrations: vit. C (25 µg L-1), Fip (600 µg L-1/1.372 µM) + Pyr (600 µg L-1/1.89 µM), and [Fip (600 µg L-1/1.372 µM) + Pyr (600 µg L-1 /1.89 µM)] + vit. C (25 µg L-1). Our results showed that insecticides can disturb the social behavior of zebrafish during 14 days of the administration, decreased the swimming performances, and elevated the oxidative stress biomarkers of SOD (superoxide dismutase), GPx (glutathione peroxidase), and MDA (malondialdehyde). The vitamin C supplement significantly attenuated the neurotoxicity of insecticide mixture and oxidative stress. This study provides possible in vivo evidence to show that vitamin C supplements could attenuate oxidative stress and brain damage of fipronil and pyriproxyfen insecticide chronic exposure on zebrafish juvenile.

Purkinje cells pathology in schizophrenia. A morphometric approach.

OBJECTIVES: Schizophrenia is a brain disorder that affects more than 21 million people worldwide. Ventricle enlargement and reduction in the volume of the temporal lobe overall and in medial temporal structures constitutes the main macroscopic findings, whilst synaptic and spinal changes as well as gliosis in the hippocampal formation, the prefrontal and the entorhinal cortex stand among cardinal microscopic findings in the schizophrenic brains. In recent years, accumulated evidence comes to light about the role of cerebellum in the pathophysiology of schizophrenia. MATERIALS AND METHODS: The present study is based on the morphological analysis and 3D neuronal reconstruction of the Purkinje cells from 10 schizophrenic brains and 10 normal controls. RESULTS: Significant morphological alterations such as loss of distal and terminal dendritic branches and decrease of the density of the dendritic spines constitute the main morphological findings found in the present study. CONCLUSIONS: The present findings may be added to accumulated evidence on macroscopic and microscopic pathology of the cerebellum in schizophrenia. Morphological alterations of Purkinje cells seem to be a central feature of neuropathology of schizophrenia, reflecting to impairment of neuronal connectivity and functionality, and related to motor and cognitive symptoms.