Proteomic approach underlying the hippocampal neurodegeneration caused by low doses of methylmercury after long-term exposure in adult rats

Bittencourt, Leonardo Oliveira; Dionízio, Aline; Nascimento, Priscila Cunha; Puty, Bruna; Leão, Luana Ketlen Reis; Luz, Diandra Araújo; Silva, Márcia Cristina Freitas; Amado, Lílian Lund; Leite, Aline L.; Buzalaf, Marília Rabelo Afonso; Crespo-López, María Elena; Maia, Cristiane do Socorro Ferraz; Lima, Rafael Rodrigues

doi:10.1039/c8mt00297e

Cited by 53 publications

(39 citation statements)

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“…The macrophage migration inhibitory factor (P30904) is a cytokine of 12.5 kD that regulates the immune response and has the expression increased in traumatic brain injuries and other pathological conditions as multiple sclerosis, meningitis and Alzheimer's disease [40][41][42][43] and it was found upregulated in our proteomic approach. It is important to highlight that cerebral injuries triggered by mechanical, immunological, diseases or even by metals insults, can also display astrocytes reactivity, that is accompanied by glial fibrillary acidic protein (GFAP, P47819) upregulation [44,45], which was observed in the exposed group. In addition, the protein S100B (P04631), found downregulated in the hippocampus of rats exposed to Pb, exerts important roles in cell metabolism and cell proliferation and differentiation [46] and its downregulation has been associated with persistently infected brains, followed by astrocytosis [47], i.e., constant glial responsiveness.…”

Section: Discussionmentioning

confidence: 99%

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Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels

Oliveira

Dionízio

Teixeira

et al. 2020

IJMS

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Lead (Pb) is an environmental and occupational neurotoxicant after long-term exposure. This study aimed to investigate the effects of systemic Pb exposure in rats from adolescence to adulthood, evaluating molecular, morphologic and functional aspects of hippocampus. For this, male Wistar rats were exposed to 50 mg/kg of Pb acetate or distilled water for 55 days by intragastric gavage. For the evaluation of short-term and long-term memories, object recognition and step-down inhibitory avoidance tests were performed. At the end of the behavioral tests, the animals were euthanized and the hippocampus dissected and processed to the evaluation of: Pb content levels in hippocampal parenchyma; Trolox equivalent antioxidant capacity (TEAC), glutathione (GSH) and malondialdehyde (MDA) levels as parameters of oxidative stress and antioxidant status; global proteomic profile and neuronal degeneration by anti-NeuN immunohistochemistry analysis. Our results show the increase of Pb levels in the hippocampus of adult rats exposed from adolescence, increased MDA and GSH levels, modulation of proteins related to neural structure and physiology and reduced density of neurons, hence a poor cognitive performance on short and long-term memories. Then, the long-term exposure to Pb in this period of life may impair several biologic organizational levels of the hippocampal structure associated with functional damages.

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Section: Discussionmentioning

confidence: 99%

“…The current protocol was previously published by our group in [44,67,68]. First, the hippocampus from two animals were pooled and each group was carried out in biologic triplicate.…”

Section: Protein Extraction Digestion and Purificationmentioning

confidence: 99%

Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels

Oliveira

Dionízio

Teixeira

et al. 2020

IJMS

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“…The proteomic analysis was performed as previously described by our group [ 11 , 82 , 83 , 84 ]. In the first step, a total of 10 animals per group were used and two samples were pooled, resulting in a final sample size of 5 per group.…”

Section: Methodsmentioning

confidence: 99%

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

Lopes

Ferreira

Davis

et al. 2020

IJMS

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Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.

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“…All proteomic analyses were performed according to protocols previously described by our group [71,72]. Firstly, the cerebellums from two animals were pooled and the analyses were carried out in triplicate.…”

Section: Proteomic Analysis: Preparation Of the Samplesmentioning

confidence: 99%

Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats

Leão

Bittencourt

Oliveira

et al. 2020

IJMS

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Lead (Pb) is an environmental contaminant that presents a high risk for human health. We aimed to investigate the possible alterations triggered by the exposure to Pb acetate for a long period in motor performance and the possible relationship with biochemical, proteomic and morphological alterations in the cerebellum of rats. Male Wistar rats were exposed for 55 days, at 50 mg/Kg of Pb acetate, and the control animals received distilled water. Open field (OF) and rotarod tests; biochemistry parameters (MDA and nitrite); staining/immunostaining of Purkinje cells (PC), mature neurons (MN), myelin sheath (MS) and synaptic vesicles (SYN) and proteomic profile were analyzed. Pb deposition on the cerebellum area and this study drove to exploratory and locomotion deficits and a decrease in the number of PC, MN, SYN and MS staining/immunostaining. The levels of MDA and nitrite remained unchanged. The proteomic profile showed alterations in proteins responsible for neurotransmitters release, as well as receptor function and second messengers signaling, and also proteins involved in the process of apoptosis. Thus, we conclude that the long-term exposure to low Pb dose promoted locomotion and histological tracings, associated with alterations in the process of cell signaling, as well as death by apoptosis.

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Proteomic approach underlying the hippocampal neurodegeneration caused by low doses of methylmercury after long-term exposure in adult rats

Abstract: Investigation of biochemical and morphological parameters underlying the cognitive dysfunction after MeHg exposure.

Cited by 53 publications

References 93 publications

Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels

Hippocampal Impairment Triggered by Long-Term Lead Exposure from Adolescence to Adulthood in Rats: Insights from Molecular to Functional Levels

Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation

Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats

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