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Microplastics (MPs), emerging environmental toxicants, have drawn attention because of their wide distribution in the environment. Exposure to MPs induces gut microbiota dysbiosis, intestinal barrier dysfunction, metabolic perturbations, and neurotoxicity in different rodents. However, the relationship between MPs, gut microbiota, and the metabolome of the gut and brain in mice remains unclear. In this study, female C57BL/6 mice were orally gavaged with vehicle, 200 nm MP, and 800 nm MP three times per week for four weeks. Cecal contents were collected for gut microbiota analysis using 16S rRNA gene sequencing. Intestinal and brain tissues from mice were used to determine metabolic profiles using liquid chromatography-mass spectrometry (LC-MS). The results showed that MP altered microbiota composition, accompanied by metabolic perturbations in the mouse gut and brain. Specifically, Firmicutes and Bacteroidetes were suggested to be important phyla for MP exposure, partially dominating further metabolite alterations. Simultaneously, MP-induced metabolic profiles were associated with energy homeostasis and bile acid, nucleotide, and carnitine metabolic pathways. The results of the mediation analysis further revealed an MP-microbiota-metabolite relationship. Our results indicate that MPs can induce gut dysbiosis and disturb metabolic dysfunction in the mouse brain and/or intestine. Integrative omics approaches have the potential to monitor MP-induced molecular responses in various organs and systematically elucidate the complex mechanisms of human health effects.

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3,4-Methylenedioximethamphetamine (MDMA; "ecstasy") is a psychotropic drug with well-known neurotoxic effects mediated by hitherto not fully understood mechanisms. The Na+- and K+-activated adenosine 5'-triphosphatase (Na+/K+ ATPase), by maintaining the ion gradient across the cell membrane, regulates neuronal excitability. Thus, a perturbation of its function strongly impacts cell homeostasis, ultimately leading to neuronal dysfunction and death. Nevertheless, whether MDMA affects the Na+/K+ ATPase remains unknown. In this study, we used synaptosomes obtained from whole mouse brain to test the effects of MDMA, three of its major metabolites [α-methyldopamine, N-methyl-α-methyldopamine and 5-(glutathion-S-yl)-α-methyldopamine], serotonin (5-HT), dopamine, 3,4-dihydroxy-L-phenylalanine (L-Dopa) and 3,4-dihydroxyphenylacetic acid (DOPAC) on the Na+/K+ ATPase function. A concentration-dependent increase of Na+/K+ ATPase activity was observed in synaptosomes exposed to the tested compounds (concentrations ranging from 0.0625 to 200 µM). These effects were independent of protein kinases A and C activities. Nevertheless, a rescue of the compounds' effects was observed in synaptosomes pre-incubated with the antioxidant N-acetylcysteine (1 mM), suggesting a role for reactive species-regulated pathways on the Na+/K+ ATPase effects. In agreement with this hypothesis, a similar increase in the pump activity was found in synaptosomes exposed to the chemical generator of superoxide radicals, phenazine methosulfate (1-250 µM). This study demonstrates the ability of MDMA metabolites, monoamine neurotransmitters, L-Dopa and DOPAC to alter the Na+/K+ ATPase function. This could represent a yet unknown mechanism of action of MDMA and its metabolites in the brain.

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Although American traditional medicine (ATM) has been practiced for millennia, its complex multi-target mechanisms of therapeutic action remain poorly understood. Animal models are widely used to elucidate the therapeutic effects of various ATMs, including their modulation of brain and behavior. Complementing rodent models, the zebrafish (Danio rerio) is a promising novel organism in translational neuroscience and neuropharmacology research. Here, we emphasize the growing value of zebrafish for testing neurotropic effects of ATMs and outline future directions of research in this field. We also demonstrate the developing utility of zebrafish as complementary models for probing CNS mechanisms of ATM action and their potential to treat brain disorders.

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Ionising radiation causes secondary tumours and/or enduring cognitive deficits, especially in children. Proton radiotherapy reduces exposure of the developing brain in children but may still cause some lasting effects. Recent observations show that ultra-high dose rate radiation treatment (≥40 Gy/s), called the FLASH effect, is equally effective at tumour control but less damaging to surrounding tissue compared with conventional dose rate protons (0.03-3 Gy/s). Most studies on the FLASH effect in brain and other tissues with different radiation modalities (electron and photon radiation), show FLASH benefits in these preclinical rodent models, but the data are limited, especially for proton FLASH, including for dose, dose rate and neurochemical and neurobehavioural outcomes. Tests of neurocognitive outcomes have been limited despite clinical evidence that this is the area of greatest concern. The FLASH effect in the context of proton exposure is promising, but a more systematic and comprehensive approach to outcomes is needed.

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Manganese (Mn) is a trace element essential for brain development and functioning of the central nervous system. However, there is a lack of information concerning the neurotoxicity of Mn under realistic doses in early stages of development, though excess of Mn results in a progressive disorder of the nervous system called manganism. In the current study, adult mice were exposed to three doses of Mn for 60 days through daily gavages, while mice pups were exposed to the same Mn doses during developmental period (gestational and breast-feeding). From the latter group of mice, a group was exposed for more 60 days to the same Mn doses. Chemical analysis revealed a dose-dependent bioaccumulation of Mn in mice's brain. Biochemical parameters revealed that (1) Mn affects non-protein thiol levels, glutathione S-tranferase and acetylcholinesterase activities, as well as the levels of oxidized lipids and proteins in mice brain, though lipids and proteins alterations were found only after exposure to high and unrealistic doses; (2) Realistic doses of Mn affects the activity of brain AChE and finally; (3) Pups' brain were affected by Mn even whether only the parental females had been previously exposed. The current study shows evidences of chemical stress in mice exposed to Mn during the early period of development and an efficient mechanism of Mn elimination under higher doses. These findings open new lines of investigation regarding manganese toxicity in vertebrates mainly in the early stages of development.

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OBJECTIVE: This study aimed at investigating radiation exposure of hippocampus in interventional medical profes sionals irradiated in the operating room, and to compare doses in the hippocampus with the effective dose (protec tion quantity), as well as with the doses measured by individual dosimeter, in order to estimate probability of reach ing levels of radiation induced cognitive and other neuropsychiatric alterations during their working career, through a Monte Carlo simulation. MATERIALS AND METHODS: A Monte Carlo simulation of hippocampal exposure was used by means of a hybrid voxel mathematical phantom of a doctor irradiated in typical angiographic projections and energy spectra inherent to interventional cardiology procedures. RESULTS: The results showed that cranial irradiation was very heterogeneous and depended on the projection: doses of left and right hippocampi may be different up to a factor of 2.5; under certain conditions, the dose of the left hippocampus may be twice the effective dose, estimated by conventional double dosimetry algorithm. CONCLUSIONS: The professional span doses of the irradiated hippocampus may overcome the threshold able to pro voke possible cognitive and emotional behavioral impairment. Therefore, in depth studies of the effects of brain irradiation in occupationally exposed interventional medical personnel appear urgently needed and crucial.

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PURPOSE: To evaluate the MR imaging findings and the usefulness of MR imaging in the diagnosis and followup of leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia. MATERIALS AND METHODS: We retrospectively evaluated the MR imaging findings of eight children with white matter abnormalities on MR out of seventeen acute leukemic patients with various neuropsychiatric symptoms who received intrathecal methotrexate administration, with or without cranial irradiation. In all cases, initial MR was performed within a week of the onset of neuropsychiatric symptoms. Follow-up MR was performed one to sixteen months after initial study, and the MR imaging findings were compared with the initial findings. RESULTS: The initial MR imaging findings were classified into three categories: focal or multifocal white matter abnormalities (3/8), and diffuse white matter abnormalities without enhancement (3/8), and diffuse white matter abnormalities with enhancement (2/8). At follow-up MR, diffuse or focal atrophic changes were noted in all children. White matter abnormalities improved in two out of three patients with focal or multifocal white matter abnormalities. In five with diffuse white matter abnormalities, the extent of these showed no significant change, but contrast enhancement was markedly reduced in two children in whom diffuse white matter abnormalities with enhancement had been demonstrated. CONCLUSION: In pediatric leukemia, the MR imaging findings of leukoencephalopathy following CNS prophylaxis therapy are variable, but are specific with the clinical history of neuropsychiatric symptoms after intrathecal methotrexate administration, with or without cranial irradiation. The MR imaging is valuable in the diagnosis and follow-up of leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia.

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PURPOSE: To evaluate the changes in arteriovenous malformation(AVM) of the brain revealed by follow-up MR images after gamma-knife surgery. MATERIALS AND METHODS: In 25 patients with AVM of the brain who had undergone gamma-knife radiosurgery, 39 MR images were obtained during follow-up between 6 and 46 months later, and were reviewed. We evaluated changes volume of the nidus and in its enhancement patterns, changes in T1- and T2-weighted images of the regions in which the nidus had disappeared, and changes in adjacent brain. Conventional follow-up cerebral angiography was performed in seven patients, and the results were correlated with those obtained by M-RI. RESULT: On the MR images obtained as described, disappearance of signal void lesion within the nidus was observed in 16 of the 25 patients. In five of 16, the nidus was obliterated within 1 year of gamma-kinfe radio-surgery, and in the remaining 11 patients this happened after 1 year. In nine cases in which the nidus remained and 16 in which it was obliterated, follow-up examination of MR images revealed spot and mixed spot-nodular enhancement, with signal void lesion. Within the nidus, serial follow-up MR images showed increased enhancement, which was nodule-like. As seen on T1-weighted images, the lesions of obliterated nidus showed slightly lower or iso- signal intensity to gray matter in all 25 cases, while T2-weighted images revealed high signal intensity in 21 cases and iso-signal intensity in four. Abnormal high signal intensity adjacent to the brain was seen on T2 weighted images in nine of 25 cases. In six of seven cases in which cerebral angiography was performed, AVM was obliterated on both MRI and angiography. In one case, however, MR imaging showed that a signal void lesion remained. Cerebral angiography in this case revealed arteriovenous shunting. CONCLUSION: After gamma-knife surgery, early follow-up revealed that in AVM of the brain, a spot and mixed spot and nodular enhancement pattern was visible, with a reduced volume of signal void lesions. During later follow-up, an enhanced nodular pattern was revealed. Nodular enhancement without signal void lesion probably indicates complete regression of the nidus of AVM.

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