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

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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Long-Term Exposure to Inorganic Mercury Leads to Oxidative Stress in Peripheral Blood of Adult Rats

Biological Trace Element Research ◽

10.1007/s12011-020-02411-5 ◽

2020 ◽

Author(s):

Victória dos Santos Chemelo ◽

Leonardo Oliveira Bittencourt ◽

Walessa Alana Bragança Aragão ◽

Sávio Monteiro dos Santos ◽

Renata Duarte Souza-Rodrigues ◽

...

Keyword(s):

Oxidative Stress ◽

Peripheral Blood ◽

Inorganic Mercury ◽

Adult Rats

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Spinal cord neurodegeneration after inorganic mercury long-term exposure in adult rats: Ultrastructural, proteomic and biochemical damages associated with reduced neuronal density

Ecotoxicology and Environmental Safety ◽

10.1016/j.ecoenv.2019.110159 ◽

2020 ◽

Vol 191 ◽

pp. 110159 ◽

Cited By ~ 7

Author(s):

Márcio Gonçalves Corrêa ◽

Leonardo Oliveira Bittencourt ◽

Priscila Cunha Nascimento ◽

Railson Oliveira Ferreira ◽

Walessa Alana Bragança Aragão ◽

...

Keyword(s):

Spinal Cord ◽

Inorganic Mercury ◽

Adult Rats ◽

Neuronal Density

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

International Journal of Molecular Sciences ◽

10.3390/ijms21103571 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3571 ◽

Cited By ~ 4

Author(s):

Luana Ketlen Reis Leão ◽

Leonardo Oliveira Bittencourt ◽

Ana Carolina Oliveira ◽

Priscila Cunha Nascimento ◽

Giza Hellen Nonato Miranda ◽

...

Keyword(s):

Synaptic Vesicles ◽

Motor Performance ◽

Second Messengers ◽

Motor Deficits ◽

Proteomic Profile ◽

Adult Rats ◽

Morphological Alterations ◽

Male Wistar Rats ◽

Mature Neurons

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5595047 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Luana Ketlen Reis Leão ◽

Leonardo Oliveira Bittencourt ◽

Ana Carolina Alves Oliveira ◽

Priscila Cunha Nascimento ◽

Maria Karolina Martins Ferreira ◽

...

Keyword(s):

Oxidative Stress ◽

Motor Cortex ◽

Wistar Rats ◽

Toxic Metal ◽

Bioinformatic Analysis ◽

Motor Dysfunction ◽

Motor Deficits ◽

Proteomic Profile ◽

Adult 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.

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

Metallomics ◽

10.1039/c8mt00297e ◽

2019 ◽

Vol 11 (2) ◽

pp. 390-403 ◽

Cited By ~ 15

Author(s):

Leonardo Oliveira Bittencourt ◽

Aline Dionizio ◽

Priscila Cunha Nascimento ◽

Bruna Puty ◽

Luana Ketlen Reis Leão ◽

...

Keyword(s):

Cognitive Dysfunction ◽

Morphological Parameters ◽

Low Doses ◽

Mehg Exposure ◽

Adult Rats ◽

Proteomic Approach ◽

Hippocampal Neurodegeneration

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

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Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

Journal of Endocrinology ◽

10.1677/joe.0.1230083 ◽

1989 ◽

Vol 123 (1) ◽

pp. 83-91 ◽

Cited By ~ 10

Author(s):

K.-L. Kolho ◽

I. Huhtaniemi

Keyword(s):

Body Weight ◽

Gnrh Agonist ◽

Gnrh Antagonist ◽

Long Term Effects ◽

Adult Rats ◽

Releasing Hormone ◽

Serum Lh ◽

Accessory Sex Organs ◽

Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

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Short-Term and Long-Term Effects of Riding for Children with Cerebral Palsy Gross Motor Functions

BioMed Research International ◽

10.1155/2018/4190249 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

L. Žalienė ◽

D. Mockevičienė ◽

B. Kreivinienė ◽

A. Razbadauskas ◽

Ž. Kleiva ◽

...

Keyword(s):

Cerebral Palsy ◽

Motor Function ◽

Long Term Effects ◽

Short Term ◽

Gross Motor ◽

Motor Functions ◽

Gross Motor Skills ◽

Gross Motor Function ◽

Group I

Aim. To evaluate the effects of riding for beginners (short-term) and advanced (long-term) riders with cerebral palsy on their whole mobility. The study involved 15 subjects (two girls and eleven boys). The subjects were aged from 3 to 19 years (8.73 years ± 5.85). All of the subjects had been diagnosed with a spastic form of cerebral palsy. The duration of the participation differed as follows: the advanced subjects had been riding for 1-4 years (2.66 years ± 1.16), while the beginners have been riding for two weeks (10 sessions). Group I (advanced riders) consisted of eight subjects (7 boys and 1 girl) who had therapy sessions regularly once a week and differed only in terms of the duration of their participation in the experiment. Group II (beginners) consisted of seven children (1 girl and 6 boys) who participated in only 10 riding sessions. All of the subjects were assessed according to the Gross Motor Function Measure (GMFM) and Gross Motor Function Classification System for CP (GMFCS) both before the investigation and after it. Conclusions. Ten riding lessons did not have an influence on the beginner riders with cerebral palsy gross motor functions and their gross motor function level did not change. However, in half of the advanced riders with cerebral palsy, the gross motor functions significantly improved. Meanwhile, the level of the performance of the gross motor skills in the four advanced riders increased, but this difference was not statistically significant.

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