Neurochemical dysfunction in motor cortex and hippocampus impairs the behavioral performance of rats chronically exposed to inorganic mercury

Teixeira, Francisco Bruno; Leão, Luana Ketlen Reis; Bittencourt, Leonardo Oliveira; Aragão, Walessa Alana Bragança; Nascimento, Priscila Cunha; Luz, Diandra Araújo; Braga, Danielle Valente; Silva, Márcia Cristina Freitas da; Oliveira, Karen Renata Matos; Herculano, Anderson Manoel; Maia, Cristiane do Socorro Ferraz; Lima, Rafael Rodrigues

doi:10.1016/j.jtemb.2018.12.008

Cited by 21 publications

(9 citation statements)

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“…Although inorganic species have unfavorable physical-chemical characteristics to biomagnify and bioaccumulate, the presence of IHg in contaminated fish commercially available and consumed by humans was already evidenced [ 6 ]. In the past few years, our group has shown that several other organs are susceptible to IHg toxicity, such as blood [ 16 ], salivary glands [ 23 ], and the central nervous structures such as the hippocampus, motor cortex, and spinal cord [ 17 , 18 , 19 , 20 , 21 ] after the exposure to 0.375 mg/kg per day of HgCl 2 . Then, despite all the toxicokinetic features, the long-term exposure to IHg increased the levels of total mercury in cerebellar parenchyma of adult rats about 4-fold higher than non-exposed animals significantly.…”

Section: Discussionmentioning

confidence: 99%

“…In this way, seeking to investigate even more the molecular features associated with IHg-induced neurotoxicity, our group has been researching the effects of IHg exposure in rats under a model that has shown to be capable of generating outcomes similar to those observed in humans, from systemic to regional analyses [ 16 , 17 , 18 , 19 , 20 , 21 ]. Moreover, some of these studies showed damages to essential areas to motor function, such as the motor cortex [ 19 , 20 , 21 ] and spinal cord [ 18 ]. However, the relationship between long-term exposure to IHg and its influence on the biochemistry and functionality of the cerebellum still lacks evidence.…”

Section: Introductionmentioning

confidence: 99%

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From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Bittencourt

Chemelo

Aragão

et al. 2021

IJMS

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Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Bittencourt

Chemelo

Aragão

et al. 2021

IJMS

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“…Although neural control of the movement starts on the prefrontal cortex and is modulated by the basal and cerebellar ganglia, the motor cortex consists of the main effector area for descending pathways and plays an essential function in fine motor control and fractionation of movement sensorimotor integration, besides acting in higher-order cognitive-motor movements [34][35][36]. Thus, considering that the motor cortex plays a fundamental role on motor function, this brain area has been extensively studied to evaluate its susceptibility to metal exposure [15,37,38].…”

Section: Discussionmentioning

confidence: 99%

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

Leão

Bittencourt

Oliveira

et al. 2021

Oxidative Medicine and Cellular Longevity

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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.

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“…Our group has shown several damages caused by mercurial exposure in experimental models evaluating salivary glands and central nervous system (Lima et al, 2018;Bittencourt et al, 2019;Corrêa et al, 2020;Freire et al, 2019;Santana et al, 2019;Teixeira et al, 2019), which are often associated with the mercury systemic distribution, that increases its levels in different organs. Moreover, despite the fact that Minamata disease is the most prominent outcome in patients with mercurial intoxication (Harada, 1995), several other disorders have also been reported in patients living in regions of mercurial exposure (Puty et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Methylmercury-induced cytotoxicity and oxidative biochemistry impairment in dental pulp stem cells: the first toxicological findings

Souza-Rodrigues

Puty

Bonfim

et al. 2021

PeerJ

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Background Methylmercury (MeHg) is a potent toxicant able to harm human health, and its main route of contamination is associated with the consumption of contaminated fish and other seafood. Moreover, dental amalgams are also associated with mercury release on human saliva and may contribute to the accumulation of systemic mercury. In this way, the oral cavity seems to be the primary location of exposure during MeHg contaminated food ingestion and dental procedures but there is a lack of literature about its effects on dental tissues and the impact of this toxicity on human health. In this way, this study aimed to analyze the effects of different doses of MeHg on human dental pulp stem cells after short-term exposure. Methods Dental pulp stem cells from human exfoliated deciduous teeth (SHED) were treated with 0.1, 2.5 and 5 µM of MeHg during 24 h. The MeHg effects were assessed by evaluating cell viability with Trypan blue exclusion assay. The metabolic viability was indirectly assessed by MTT reduction assay. In order to evaluate an indicative of antioxidant defense impairment, cells exposed to 0.1 and 5 µM MeHg were tested by measuring glutathione (GSH) level. Results It was observed that cell viability decreased significantly after exposure to 2.5 and 5 µM of MeHg, but the metabolic viability only decreased significantly at 5 µM MeHg exposure, accompanied by a significant decrease in GSH levels. These results suggest that an acute exposure of MeHg in concentrations higher than 2.5 µM has cytotoxic effects and reduction of antioxidant capacity on dental pulp stem cells.

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Neurochemical dysfunction in motor cortex and hippocampus impairs the behavioral performance of rats chronically exposed to inorganic mercury

Cited by 21 publications

References 57 publications

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

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

Methylmercury-induced cytotoxicity and oxidative biochemistry impairment in dental pulp stem cells: the first toxicological findings

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