An exploratory study on the ability of manganese to supplement rotenone neurotoxicity in rats.

Parkinson's disease (PD) is a complex disorder, primarily of idiopathic origin, with environmental stressors like rotenone and manganese linked to its development. This study explores their potential interaction and resulting neurotoxicity, aiming to understand how environmental factors contribute to PD. In an eight-day experiment, male Wistar rats weighing 280-300 g were subjected to rotenone, manganese, or a combination of both. Various parameters were assessed, including body weight, behavior, serum markers, tissue damage, protein levels (tyrosine hydroxylase, Dopamine- and cAMP-regulated neuronal phosphoprotein -DARPP-32-, and α-synuclein), and mitochondrial function. Manganese heightened rotenone's impact on reducing food intake without causing kidney or liver dysfunction. However, the combined exposure intensified neurotoxicity, which was evident in augmented broken nuclei and decreased tyrosine hydroxylase and DARPP-32 levels in the striatum. While overall mitochondrial function was preserved, co-administration reduced complex IV activity in the midbrain and liver. In conclusion, our findings revealed a parallel toxic effect induced by rotenone and manganese. Notably, while these substances do not target the same dopaminergic regions, a notable escalation in toxicity is evident in the striatum, the brain region where their toxic effects converge. This study highlights the need for further exploration regarding the interaction of environmental factors and their possible impact on the etiology of PD.

Biochemical changes and bioaccumulation of manganese in Astyanax lacustris (Teleostei: Characidae).

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris.

Nondestructive Evaluation of Metal Bioaccumulation and Biochemical Biomarkers in Blood of Broad-Snouted Caiman (Caiman latirostris) from Northeastern Brasil.

Studies on the bioaccumulation and toxicity of contaminants in Crocodylians are scarce. We evaluated alterations in concentrations of the nondestructive biomarkers butyrylcholinesterase (BChE), glutathione-S-transferase (GST), superoxide dismutase (SOD), and reduced glutathione (GSH), together with bioaccumulation of the metals iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), chronium (Cr), aluminium (Al), and lead (Pb) in Caiman latirostris captured in Tapacurá Reservoir (TR; São Lourenço da Mata, Pernambuco, Brasil), in urbanized areas of Pernambuco State (UA; Brasil) and from the AME Brasil caiman farm (AF; Marechal Deodoro, Alagoas, Brasil); the latter was used as a potential reference with low levels of contamination. For metal analysis, 500 µL of blood was digested in 65% HNO3 and 30% H2O2. The samples were analyzed by inductively coupled plasma-optical emission spectrometry. For analysis of biomarkers, an aliquot of blood was centrifuged to obtain plasma in which biochemical assays were performed. Blood concentrations of metals analyzed in animals from AF were lower compared with TR and UA, confirming that animals from the caiman farm could be used as references with low levels of contamination. Iron, Cu, Mn, Al, and Pb exceeded toxic levels for other vertebrates in animals from TR and UA. Butyrylcholinesterase activity showed significant reduction in adults from UA and TR compared with AF. An increase in the activity of GST and GSH, in adults of TR and UA in relation to AF, was verified. Superoxide dismutase activity showed a significant reduction in adults of TR in relation to AF, and the concentrations of Cu and Mn were negatively correlated with SOD activity. Animals from UA and TR showed greater concentrations of the analyzed metals compared with reference animals, and changes in biomarkers were seen, confirming the potential of these nondestructive chemical and biological parameters in blood of C. latirostris for biomonitoring of pollution. Environ Toxicol Chem 2024;43:878-895. © 2024 SETAC.

Probucol neuroprotection against manganese-induced damage in adult Wistar rat brain slices.

Manganese (Mn) is an abundant element used for commercial purposes and is essential for the proper function of biological systems. Chronic exposure to high Mn concentrations causes Manganism, a Parkinson's-like neurological disorder. The pathophysiological mechanism of Manganism remains unknown; however, it involves mitochondrial dysfunction and oxidative stress. This study assessed the neuroprotective effect of probucol, a hypolipidemic agent with anti-inflammatory and antioxidant properties, on cell viability and oxidative stress in slices of the cerebral cortex and striatum from adult male Wistar rats. Brain structure slices were kept separately and incubated with manganese chloride (MnCl2) and probucol to evaluate the cell viability and oxidative parameters. Probucol prevented Mn toxicity in the cerebral cortex and striatum, as evidenced by the preservation of cell viability observed with probucol (10 and 30 µM) pre-treatment, as well as the prevention of mitochondrial complex I inhibition in the striatum (30 µM). These findings support the protective antioxidant action of probucol, attributed to its ability to prevent cell death and mitigate Mn-induced mitochondrial dysfunction.

In vitro evaluation of the cytotoxic and genotoxic effects of Al and Mn in ambient concentrations detected in groundwater intended for human consumption.

Environmental exposure to metals can induce cytotoxic and genotoxic effects in cells and affect the health of the exposed population. To investigate the effects of aluminum (Al) and manganese (Mn), we evaluated their cytogenotoxicity using peripheral blood mononuclear cells (PBMCs) exposed to these metals at previously quantified concentrations in groundwater intended for human consumption. The cell viability, membrane integrity, nuclear division index (NDI), oxidative stress, cell death, cell cycle, and DNA damage were analyzed in PBMCs exposed to Al (0.2, 0.6, and 0.8 mg/L) and Mn (0.1, 0.3, 1.0, and 1.5 for 48 h. We found that Al induced late apoptosis; decreased cell viability, NDI, membrane integrity; and increased DNA damage. However, no significant alterations in the early apoptosis, cell cycle, and reactive oxygen species levels were observed. In contrast, exposure to Mn altered all evaluated parameters related to cytogenotoxicity. Our data show that even concentrations allowed by the Brazilian legislation for Al and Mn in groundwater intended for human consumption cause cytotoxic and genotoxic effects in PBMCs. Therefore, in view of the results found, a comprehensive approach through in vivo investigations is needed to give robustness and validity to the results obtained, thus broadening the understanding of the impacts of metals on the health of environmentally exposed people.

Prenatal manganese biomarkers and operant test battery performance in Mexican children: Effect modification by child sex.

BACKGROUND: Manganese (Mn) is essential to healthy neurodevelopment, but both Mn deficiency and over-exposure have been linked to prefrontal cortex (PFC) impairments, the brain region that regulates cognitive and neurobehavioral processes responsible for spatial memory, learning, motivation, and time perception. These processes facilitated by attention, inhibitory control, working memory, and cognitive flexibility are often sexually dimorphic and complex, driven by multiple interconnected neurologic and cognitive domains. OBJECTIVE: We investigated the role of child sex as an effect modifier of the association between prenatal Mn exposure and performance in an operant testing battery (OTB) that assessed multiple cognitive and behavioral functional domains. METHODS: Children (N = 575) aged 6-8 years completed five OTB tasks. Blood and urinary Mn measurements were collected from mothers in the 2nd and 3rd trimesters. Multiple regression models estimated the association between Mn biomarkers at each trimester with OTB performance while adjusting for socio-demographic covariates. Covariate-adjusted weighted quantile sum (WQS) regression models were used to estimate the association of a Mn multi-media biomarker (MMB) mixture with OTB performance. Interaction terms were used to estimate modification effect by child sex. RESULTS: Higher blood Mn exposure was associated with better response rates (more motivation) on the progressive ratio task and higher overall accuracy on the delayed matching-to-sample task. In the WQS models, the MMB mixture was associated with better response rates (more motivation) on the progressive ratio task. Additionally, for the linear and WQS models, we observed a modification effect by child sex in the progressive ratio and delayed matching-to-sample tasks. Higher prenatal Mn biomarker levels were associated with improved task performance for girls and reduced performance in boys. CONCLUSION: Higher prenatal blood Mn concentrations and the MMB mixture predicted improved performance on two of five operant tasks. Higher prenatal Mn concentrations regulated executive functions in children in a sexually dimorphic manner. Higher prenatal Mn exposure is associated with improved performance on spatial memory and motivation tasks in girls, suggesting that Mn's nutritional role is sexually dimorphic, and should be considered when making dietary and/or environmental intervention recommendations.

Manganese Exposure Induces Cellular Aggregates and the Accumulation of ß-Catenin in Skin of Zebrafish Embryos.

The effects of manganese (Mn) toxicity in different organs and tissues in humans and other vertebrates have been studied since the beginning of the past century, but most of its cellular effects remain largely unknown. In this study, we studied the effects of Mn in zebrafish, at the cellular level, due to the transparent nature of zebrafish larvae that enables a powerful analysis under the light microscope. The collection of our results shows that environmental concentrations of 0.5 mg/L affect swim bladder inflation; at concentration of 50 and 100 mg/L Mn (1) induces alterations in viability, swim bladder, heart, and size of zebrafish larvae, (2) induces an increase in melanocyte area and the formation of cellular aggregates in the skin, and (3) induces an accumulation of ß-Catenin in mesenchymal cells in the caudal fin of zebrafish larvae. Our data suggest that increased levels of Mn induce cell aggregate formation in the skin and the presence of more melanocytes in the zebrafish caudal fin. Interestingly, the adhesion protein ß-Catenin was activated in mesenchymal cells near the cell aggregates. These results open important new questions on the role of Mn toxicity on cellular organization and ß-Catenin responses in fishes.

Multiple biomarkers response of Astyanax lacustris (Teleostei: Characidae) exposed to manganese and temperature increase.

The present study aimed to evaluate the toxicity of Mn (6.65 mg/L) at different exposure times (96 h, 7, 14, and 21 days) and evaluate its possible toxic effects on the fish Astyanax lacustris through multi-biomarkers and the maximum critical temperature (CT Max). The results show an increase in the Mn accumulation (liver and gills) with increasing exposure time. The glutathione S-transferase (GST) activity showed differences in the group exposed to Mn for 96 h compared to the group exposed for 21 days. The acetylcholinesterase (AChE) activity increased in the fish exposed for 7 days compared to the control group. On the other hand, no genotoxic changes were observed. The CT Max showed that the loss of equilibrium of 50% of the fish occurs at a temperature of 39ºC, with and without the Mn presence. Furthermore, the catalase gene expression (oxidative stress) did not show alterations.

Neuroprotective Effect of Vitamin D on Behavioral and Oxidative Parameters of Male and Female Adult Wistar Rats Exposed to Mancozeb (manganese/zinc ethylene bis-dithiocarbamate).

The constant exposure of rural workers to pesticides is a serious public health problem. Mancozeb (MZ) is a pesticide  linked to hormonal, behavioral, genetic, and neurodegenerative effects, mainly related to oxidative stress. Vitamin D is a promising molecule that acts as a protector against brain aging. This study aimed to evaluate the neuroprotective role of vitamin D in adult male and female Wistar rats exposed to MZ. Animals received 40 mg/kg of MZ i.p. and 12.5 µg/kg or 25 µg/kg vitamin D by gavage, twice a week, for 6 weeks. The concentration of manganese had a significant increase in the hippocampus of both sexes and in the striatum of females, unlike zinc, which did not show a significant increase. MZ poisoning led to mitochondrial changes in brain tissues and promoted anxiogenic effects, especially in females. Alterations in antioxidant enzymes, mainly in the catalase activity were observed in intoxicated rats. Taken together, our results showed that exposure to MZ leads to the accumulation of manganese in brain tissues, and the behavior and metabolic/oxidative impairment were different between the sexes. Furthermore, the administration of Vitamin D was effective in preventing the damage caused by the pesticide.

Subcellular distribution and physiological responses of native and exotic grasses from the Pampa biome subjected to excess manganese.

Fungicides containing manganese (Mn) applied to control plant diseases increase the concentration of Mn in soils, which may potentiate Mn toxicity in acid soils. Some species of wild grasses, such as those from the Pampa biome located in South America, or even those introduced into this biome, may possess different mechanisms of tolerance to excess Mn. The present study aimed to evaluate the subcellular distribution and physiological and biochemical responses of exotic and native grasses from the Pampa biome, cultivated in Mn excess. The experiment was conducted in nutrient solution in a greenhouse, in an entirely randomized design, bifactorial 4 × 4, consisting of four Mn concentrations (2 [control], 300, 600 and 900 µM) and four species (two exotic: Avena strigosa and Lolium multiflorum; and two native: Paspalum notatum and Paspalum plicatulum). At 27 days of exposure to the treatments, biomass and growth rates, leaf gas exchange with the environment, photosynthetic pigment concentrations of malondialdehyde and H2O2, antioxidant enzyme activities (SOD and POD), and subcellular distribution of Mn were evaluated. Most of the grasses showed high concentration of Mn in tissues, mainly, in the shoot. In the presence of 900 µM Mn, more than 80% of the absorbed Mn was compartmentalized in the cell walls and vacuoles of the cells. Compartmentalization of Mn excess into metabolically less active organelles is the main tolerance factor in grasses. Physiological and biochemical responses were stimulated in the presence of 300 µM Mn, while 900 µM Mn negatively affected biochemical-physiological responses of grasses. The species L. multiflorum was most sensitive to excess Mn, while P. notatum was the most tolerant.

Synergic control in asymptomatic welders during multi-finger force exertion and load releasing while standing.

Motor synergies, i.e., neural mechanisms that organize multiple motor elements to ensure stability of actions, are affected by several neurological condition. Asymptomatic welders showed impaired synergy controlling the stability of multi-finger action compared to non-welders and this impairment was associated with microstructural damage in the globus pallidus. We further explored the effect of welding-related metal exposure on multi-finger synergy and extended our investigation to posture-stabilizing synergy during a standing task. Occupational, MRI, and performance-stabilizing synergies during multi-finger accurate force production and load releasing while standing were obtained from 29 welders and 19 age- and sex-matched controls. R2* and R1 relaxation rate values were used to estimate brain iron and manganese content, respectively, and diffusion tensor imaging was used to reflect brain microstructural integrity. Associations of brain MRI (caudate, putamen, globus pallidus, and red nucleus), and motor synergy were explored by group status. The results revealed that welders had higher R2* values in the caudate (p = 0.03), putamen (p = 0.01), and red nucleus (p = 0.08, trend) than controls. No group effect was revealed on multi-finger synergy index during steady-state phase of action (ΔVZss). Compared to controls, welders exhibited lower ΔVZss (-0.106 ± 0.084 vs. 0.160 ± 0.092, p = 0.04) and variance that did not affect the performance variable (VUCM, 0.022 ± 0.003 vs. 0.038 ± 0.007, p = 0.03) in the load releasing, postural task. The postural synergy index, ΔVZss, was associated negatively with higher R2* in the red nucleus in welders (r = -0.44, p = 0.03), but not in controls. These results suggest that the synergy index in the load releasing during a standing task may reflect welding-related neurotoxicity in workers with chronic metals exposure. This finding may have important clinical and occupational health implications.

Prenatal Co-Exposure to Manganese, Mercury, and Lead, and Neurodevelopment in Children during the First Year of Life.

Lead (Pb), mercury (Hg), and manganese (Mn) are neurotoxic, but little is known about the neurodevelopmental effects associated with simultaneous prenatal exposure to these metals. We aimed to study the associations of Pb, Hg, and Mn prenatal levels (jointly and separately) with neurodevelopment in the first year of life. Methods: Pb, Hg, and Mn blood lead levels were measured in 253 pregnant women. Their offspring's neurodevelopment was assessed through the Bayley Scale of Infant Development III® at one, three, six, and twelve months. The metals' mean blood levels (µg/L) were Pb = 11.2, Hg = 2.1, and Mn = 10.2. Mean language, cognitive, and motor development scores of the infants at each age were between low-average and average. Multilevel models' results showed that language development coefficients of the offspring decreased by 1.5 points per 1 µg/dL increase in maternal blood lead levels (p = 0.002); the magnitude of the aforementioned association increased in children with maternal blood Mn < 9.6 µg/L (ß = -1.9, p = 0.003) or Hg > 1.9 µg/L (ß = -1.6, p = 0.013). Cognitive and motor development had negative associations with maternal blood Pb levels; the latter was statistically significant when the interaction term between Pb, Mn, and Hg was included (ß = -0.037, p = 0.03). Prenatal exposure to low Pb levels may impair infants' neurodevelopment in the first year of life, even more so if they are exposed to Hg or deficient in Mn.

Risk evaluation of occupational exposure of southern Brazilian flower farmers to pesticides potentially leading to cholinesterase inhibition and metals exposure.

This work presents a frequency matched observational study comparing flower farmers exposed to pesticides and unexposed individuals as controls. All subjects were interviewed before plasma and urine collection. Manganese and Zinc were measured in theses samples by using dynamic reaction cell inductively coupled mass spectrometry. Cholinesterase activity was analyzed through spectrophotometry by using a modified version of the Ellman method. Seventy-eight percent of subjects reported occupational contact with pesticides, from which 37% reported exposure for over 9 years. Flower farms farmers had increased odds of having headache and irritability, respectively, by factors of 6.2 and 2.4 than the control subjects. While the odds of exposed subjects to have insomnia was smaller than control subjects by a factor of 0.34. Exposure to pesticides had a significant effect regarding the plasmatic plasma and urinary manganese levels and whole blood cholinesterase activity (p < 0.05). High levels of plasma and urinary manganese, as well as cholinesterase inhibition in whole blood, were evident in the flower farmers who participated in the study.

Environmentally relevant manganese concentrations evoke anxiety phenotypes in adult zebrafish.

Manganese (Mn) is an essential metal for living organisms. However, the excess of Mn can be toxic, especially for the central nervous system. Herein, we used adult zebrafish as model organism to investigate the relationship of an environmentally relevant Mn exposure with the onset of neurobehavioral disturbances and brain biochemical alterations. Fish were exposed to MnCl2 at 0.5, 2.0, 7.5 and 15.0 mg/L for 96 h, and after submitted to trials for examining exploratory, locomotor and anxiety-related behaviors. The neurobehavioral parameters were followed by the analyses of cell viability, Mn accumulation and acetylcholinesterase activity in the brain, and whole-body cortisol levels. By Novel tank, Light dark and Social preference test, we found that the exposure to Mn, along with locomotor deficits induced anxiety-like phenotypes in zebrafish. Most of these behavioral changes were evoked by the highest concentrations, which also caused cell viability loss, higher accumulation of Mn and increased AChE activity in the brain, and an increase in the whole-body cortisol content. Our findings demonstrated that zebrafish are quite sensitive to levels of Mn found in the environment, and that the magnitude of the neurotoxic effects may be associated with the levels of manganese accumulated in the brain. Interestingly, we showed that Mn exposure in addition to motor deficits may also cause psychiatric abnormalities, namely anxiety.

Protective Effects of Probucol on Different Brain Cells Exposed to Manganese.

Manganese (Mn) is an essential metal for many functions in the body. However, in excess, it can be neurotoxic and cause a Parkinson-like syndrome, known as manganism. Here, we aimed to identify a protective effect of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, against Mn-induced toxicity in human neuroblastoma (SH-SY5Y) and glioblastoma (C6) cell lines. The cells were incubated with increasing concentrations of Mn followed by probucol addition 1, 3, 6, and/or 24 h to assess the metal toxic doses and measure the protective effect of probucol against Mn-induced oxidative damage. Longer exposition to Mn showed decreased SH-SY5Y cellular viability in concentrations higher than 100 µM, and probucol was able to prevent this effect. The C6 cells were more sensitive to the Mn deleterious actions, decreasing the cell viability after 6 h of 500 µM Mn exposure. In addition, probucol prevents the complex I and II of the mitochondrial respiratory chain (MRC) inhibition caused by Mn and decreased the intracellular ROS production. Taken together, our results showed that Mn toxicity affects differently both cell lines and probucol has a protective effect against the oxidative imbalance in the central nervous system.

Individual and Combined Effects of Manganese and Chromium on a Freshwater Chlorophyceae.

Manganese (Mn), an essential metal in trace amounts, and chromium (Cr), a nonessential metal to algae, are often found in effluent discharges and may co-occur in contaminated aquatic environments. Therefore, we investigated the effects of Mn and Cr, and their mixtures, on a freshwater Chlorophyceae, Raphidocelis subcapitata, using a multiple endpoint approach. Regarding the single exposure of metals, Mn was 4 times more toxic (median inhibitory concentration at 72 h [IC5072 h ] = 4.02 ± 0.45 µM Mn) than Cr (IC5072 h = 16.42 ± 4.94 µM Cr) for microalgae, considering the effects on the relative growth rate. Moreover, this species was the most sensitive to Mn, according to the species sensitivity distribution curve. Overall, the tested metals did not lead to significant changes in reactive oxygen species production, cellular complexity, and cell relative size but significantly decreased the algal growth and the mean cell chlorophyll a (Chl a) fluorescence at the highest concentrations (3.64-14.56 µM of Mn and 15.36-19.2 µM of Cr). The decreased mean cell Chl a fluorescence indicates an impact on pigment synthesis, which may be related to the observed growth inhibition. In the mixture tests, the reference models concentration addition and independent action were used to analyze the data, and the independent action model was the best fit to describe our results. Therefore, the Mn and Cr mixture was noninteractive, showing additive effects. This is the first study to address the combined toxicity of Mn and Cr regarding freshwater Chlorophyceae. Environ Toxicol Chem 2022;41:1004-1015. © 2022 SETAC.

Do Manganese and Iron in Association Cause Biochemical and Genotoxic Changes in Oreochromis Niloticus (Teleostei: Cichlidae)?

The present study aimed to evaluate the toxicity of the association between Fe and Mn in Oreochromis niloticus through genotoxic (micronucleus test and comet assay) and biochemical (CAT and GST enzymes) assays. The tested treatments were T1 = control group (without metal addition), T2 = 2.60 mg L-1 of Fe + 0.2 mg L-1 of Mn, and T3 = 4.40 mg L-1 of Fe + 3.49 mg L-1 of Mn, during 96-h bioassays. All animals exposed to the metals showed a significant increase in erythrocyte micronucleus frequency and DNA damage. The hepatic GST activity increased two times in animals exposed to T3 compared to the control group. The results indicate that Fe + Mn caused genotoxic and biochemical changes in exposed fish. Therefore, excess metals in ecosystems, even those essential for organisms, can be dangerous for the local biota due to the risk associated with high concentrations of these metals.

Wide visible-range activatable fluorescence ZnSe:Eu3+/Mn2+@ZnS quantum dots: local atomic structure order and application as a nanoprobe for bioimaging.

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu3+/Mn2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu3+/Mn2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu3+ concentration at a fixed amount of Mn2+, systematically enhancing the Mn2+ emission intensity via energy transfer from the Eu3+ to Mn2+ ion. The ZnSe:Eu3+/Mn2+@ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

Environmental and occupational exposure to metals (manganese, mercury, iron) and Parkinson's disease in low and middle-income countries: a narrative review.

OBJECTIVES: We designed and conducted a narrative review consistent with the PRISMA guidelines (PROSPERO registration number: CRD42018099498) to evaluate the association between environmental metals (manganese, mercury, iron) and Parkinson's Disease (PD) in low and middle-income countries (LMIC). METHODS: Data sources: A total of 19 databases were screened, and 2,048 references were gathered. Study selection: Randomized controlled trials, cluster trials, cohort studies, case-control studies, nested case-control studies, ecological studies, cross-sectional studies, case series, and case reports carried out in human adults of LMIC, in which the association between at least one of these three metals and the primary outcome were reported. Data extraction: We extracted qualitative and quantitative data. The primary outcome was PD cases, defined by clinical criteria. A qualitative analysis was conducted. RESULTS: Fourteen observational studies fulfilled the selection criteria. Considerable variation was observed between these studies' methodologies for the measurement of metal exposure and outcome assessment. A fraction of studies suggested an association between the exposure and primary outcome; nevertheless, these findings should be weighted and appraised on the studies' design and its implementation limitations, flaws, and implications. CONCLUSIONS: Further research is required to confirm a potential risk of metal exposure and its relationship to PD. To our awareness, this is the first attempt to evaluate the association between environmental and occupational exposure to metals and PD in LMIC settings using the social determinants of health as a framework.

Critical Involvement of Glial Cells in Manganese Neurotoxicity.

Over the years, most of the research concerning manganese exposure was restricted to the toxicity of neuronal cells. Manganese is an essential trace element that in high doses exerts neurotoxic effects. However, in the last two decades, efforts have shifted toward a more comprehensive approach that takes into account the involvement of glial cells in the development of neurotoxicity as a brain insult. Glial cells provide structural, trophic, and metabolic support to neurons. Nevertheless, these cells play an active role in adult neurogenesis, regulation of synaptogenesis, and synaptic plasticity. Disturbances in glial cell function can lead to neurological disorders, including neurodegenerative diseases. This review highlights the pivotal role that glial cells have in manganese-induced neurotoxicity as well as the most sounding mechanisms involved in the development of this phenomenon.