Morphographic Changes in the Electrocardiogram of Colossoma macropomum Caused by Exposure to Manganese.

Manganese (Mn2+) is an abundant chemical element in the earth's crust and is present in soil, water, and industrial environments, including mining, welding, and battery manufacturing. Manganese (Mn) is an essential metal needed as a cofactor for many enzymes to maintain proper biological functions. Excessive exposure to Mn in high doses can result in a condition known as manganism, which results in disorders of the neurological, cardiac, and pulmonary systems. The aim of this study was to assess cardiac susceptibility to manganese intoxication in Colossoma macropomum subjected to a fixed concentration of 4 mg/mL for a period of up to 96 h. This study used 45 Tambaquis (30.38 ± 3.5 g) divided into five groups of 9 animals/treatment. The treated groups were exposed to the manganese concentration for a period of 24, 48, 72, and 96 h, after which the animals' ECGs were recorded, showing heart rate, R-R interval, P-Q interval, QRS complex duration and S-T interval. The results showed that cardiac activity decreased as the contact time increased, with an increase in the P-Q and S-T intervals. This indicates that the breakdown of circulatory homeostasis in these animals was caused by contact time with manganese.

Recording of hippocampal activity on the effect of convulsant doses of caffeine.

Seizures occur when there is a hyper-excitation of the outer layer of the brain, with subsequent excessive synchrony in a group of neurons. According to the World Health Organization (WHO), an estimated 50 million people are affected by this disease, a third of whom are resistant to the treatments available on the market. Caffeine (1,3,7-trimethylxanthine), which belongs to the purine alkaloid family, is the most widely consumed psychoactive drug in the world. It is ingested by people through drinks containing this substance, such as coffee, and as an adjuvant in analgesic therapy with non-steroidal antiflammatory drugs. The present study evaluated the electrocorticographic changes observed in the hippocampus of Wistar rats subjected to acute doses of caffeine (150 mg/kg i.p), which represents a toxic dose of caffeine corresponding to an estimated acute intake of more than 12 cups of coffee to record its convulsant activity. Our results showed, for the first time, that the administration of high doses of caffeine (150 mg/kg i.p.) in rats caused an increase in the spectral distribution of power in all frequency bands and suggested the appearance of periods of ictal and interictal peaks in the electrocorticogram (ECog). We have also shown that the anticonvulsants phenytoin, diazepam and phenobarbital have a satisfactory response when associated with caffeine.

Global Scientific Research Landscape on Aluminum Toxicology.

This study aimed to identify the landscape of current aluminum toxicity based on knowledge mapping of the 100 most-cited articles on toxicological aspects of aluminum in biological organisms. The research was searched in the Web of Science Core Collection (WoS-CC) with publications between 1945 and 2022. Data regarding authorship, title, journal, year of publication, citation count, country, keywords, study design, and research hotspots were extracted and all elected articles were analyzed. Our results showed that among the articles selected, literature review and in vivo studies were the most common study designs. The USA and England were found as the countries with most publications. Alzheimer's disease (AD), aluminum, and neurotoxicity were found as the most frequent keywords. The articles most cited in world literature suggested that aluminum exposure is associated with Alzheimer's disease, Parkinson's disease (PD), dialysis encephalopathy, amyotrophic lateral sclerosis, neurodegeneration changes, cognitive impairment, such as bone damage, oxidative alterations, and cytotoxicity.

Exposure to tolerable concentrations of aluminum triggers systemic and local oxidative stress and global proteomic modulation in the spinal cord of rats.

The tolerable aluminum (Al) intake levels for humans are constantly under review by regulatory agencies due to novel pre-clinical evidence on the neurotoxicity of prolonged Al exposure; however, little is known about the effects of Al on the spinal cord. This study aimed to investigate potential adverse effects on both spinal cord and systemic biochemical balance after prolonged exposure to a low dose of Al. Twenty adult rats were distributed in the control (distilled water) and exposed group (8.3 mg of AlCl3/kg/day). After 60 days, both blood and spinal cord samples were collected for oxidative stress and proteomic analyses. In plasma and erythrocytes, glutathione level was not different between groups; however, exposure to AlCl3 significantly decreased glutathione level in the spinal cord. Thiobarbituric acid reactive substances levels in the plasma and spinal cord of animals from the control group were significantly lower than those animals exposed to AlCl3. Exposure to AlCl3 significantly modulated the expression of proteins associated with the cell cycle, stimulus-response, cytoskeleton, nervous system regulation, protein activity, and synaptic signaling. Therefore, prolonged exposure to a low dose of Al triggered oxidative stress and proteomic changes that may affect spinal cord homeostasis.

Global Proteomic Profile of Aluminum-Induced Hippocampal Impairments in Rats: Are Low Doses of Aluminum Really Safe?

Hippocampus is the brain area where aluminum (Al) accumulates in abundance and is widely associated with learning and memory. In the present study, we evaluate behavioral, tissue, and proteomic changes in the hippocampus of Wistar rats caused by exposure to doses that mimic human consumption of aluminum chloride (AlCl3) in urban areas. For this, male Wistar rats were divided into two groups: Control (distilled water) and AlCl3 (8.3 mg/kg/day), both groups were exposed orally for 60 days. After the Al exposure protocol, cognitive functions were assessed by the Water maze test, followed by a collection for analysis of the global proteomic profile of the hippocampus by mass spectrometry. Aside from proteomic analysis, we performed a histological analysis of the hippocampus, to the determination of cell body density by cresyl violet staining in Cornu Ammonis fields (CA) 1 and 3, and hilus regions. Our results indicated that exposure to low doses of aluminum chloride triggered a decreased cognitive performance in learning and memory, being associated with the deregulation of proteins expression, mainly those related to the regulation of the cytoskeleton, cellular metabolism, mitochondrial activity, redox regulation, nervous system regulation, and synaptic signaling, reduced cell body density in CA1, CA3, and hilus.

Deciphering the Global Proteomic Profile Involved in Methylmercury-Induced Cerebellar Neurodegeneration and Motor Dysfunction in Adult Rats.

Mercury is a ubiquitous pollutant in the environment with potential neurotoxic effects. Several populations are susceptible to mercurial exposure, especially methylmercury (MeHg) at low doses for long periods through food consumption. Given this, the present work aimed to assess the effects of long-term MeHg exposure on the cerebellum of rats from a translational perspective using a representative dose, assessing molecular, biochemical, morphological, and behavioral parameters. The model was produced by administering 40 µg/kg of MeHg for 60 days to adult male Wistar rats by oral gavage. As a result of this exposure, the animals presented motor deficits in open field and rotarod tests which were associated with an increase in total mercury content in cerebellar parenchyma, a reduction in antioxidant competence against peroxyl radicals, and increased nitrite and lipid peroxidation levels. The proteomic approach showed 317 modulated proteins. Such findings were associated with reductions in mature neuron and Purkinje cell densities and glial fibrillary acidic protein immunostained areas and increased microglial density. In addition, decreases in myelin basic protein and synaptophysin immunostaining were also observed. The results thus provided new evidence of the mechanisms underlying complex MeHg-induced neurodegeneration, especially the proteins underlying the biochemical and morphological features associated with motor dysfunction.

Methylmercury exposure during prenatal and postnatal neurodevelopment promotes oxidative stress associated with motor and cognitive damages in rats: an environmental-experimental toxicology study.

The environmental contamination by methylmercury (MeHg) is a major concern for public health. The effects of MeHg in the central nervous system (CNS) of adult animals have been extensively investigated; however, little is known about the effects of MeHg exposure during intrauterine and lactation periods on motor and cognitive functions of adolescent rats. Therefore, this study aimed to investigate the effect of MeHg exposure during intrauterine life and lactation on both motor and cognitive functions of offspring rats. Ten female Wistar rats were exposed to 40 µg/kg/day of MeHg through cookie treats from the first day of pregnancy until the last day of breastfeeding. Both motor and cognitive functions of offspring male rats were assessed by open field, rotarod, and step-down inhibitory avoidance tests. Forty-one days after birth, the hippocampus and cerebellum were collected to determine total Hg content, antioxidant capacity against peroxyl radicals (ACAP), reduced glutathione (GSH) levels, lipid peroxidation (LPO), and nitrite levels. MeHg exposure during CNS development increased Hg levels in both hippocampal and cerebellar parenchymas, triggered oxidative stress throughout ACAP and GSH decrease, increased LPO and nitrite levels. These alterations resulted in reduced spontaneous and stimulated locomotion and short- and long-term memory deficits. Therefore, damages triggered by MeHg exposure during intrauterine life and lactation had detrimental effects on oxidative biochemistry and motor and cognitive functions of offspring rats.

Methylmercury Causes Neurodegeneration and Downregulation of Myelin Basic Protein in the Spinal Cord of Offspring Rats after Maternal Exposure.

Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 µg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats.

Lead-Induced Motor Dysfunction Is Associated with Oxidative Stress, Proteome Modulation, and Neurodegeneration in Motor Cortex of Rats.

Lead (Pb) is a toxic metal with great neurotoxic potential. The aim of this study was to investigate the effects of a long-term Pb intoxication on the global proteomic profile, oxidative biochemistry and neuronal density in motor cortex of adult rats, and the possible outcomes related to motor functions. For this, Wistar rats received for 55 days a dose of 50 mg/Kg of Pb acetate by intragastric gavage. Then, the motor abilities were evaluated by open field and inclined plane tests. To investigate the possible oxidative biochemistry modulation, the levels of pro-oxidant parameters as lipid peroxidation and nitrites were evaluated. The global proteomic profile was evaluated by ultraefficiency liquid chromatography system coupled with mass spectrometry (UPLC/MS) followed by bioinformatic analysis. Moreover, it was evaluated the mature neuron density by anti-NeuN immunostaining. The statistical analysis was performed through Student's t-test, considering p < 0.05. We observed oxidative stress triggering by the increase in malonaldehyde and nitrite levels in motor cortex. In the proteomic analysis, the motor cortex presented alterations in proteins associated with neural functioning, morphological organization, and neurodegenerative features. In addition, it was observed a decrease in the number of mature neurons. These findings, associated with previous evidences observed in spinal cord, cerebellum, and hippocampus under the same Pb administration protocol, corroborate with the motor deficits in the rats towards Pb. Thus, we conclude that the long-term administration to Pb in young Wistar rats triggers impairments at several organizational levels, such as biochemical and morphological, which resulted in poor motor performance.