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.

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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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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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Fetal Transplants Rescue Axial Muscle Representations in M1 Cortex of Neonatally Transected Rats That Develop Weight Support

Journal of Neurophysiology ◽

10.1152/jn.1998.80.6.3021 ◽

1998 ◽

Vol 80 (6) ◽

pp. 3021-3030 ◽

Cited By ~ 30

Author(s):

Simon F. Giszter ◽

William J. Kargo ◽

Michelle Davies ◽

Motohide Shibayama

Keyword(s):

Spinal Cord ◽

Motor Cortex ◽

Body Representation ◽

Motor Deficits ◽

Motor Representation ◽

Adult Rats ◽

Axial Muscles ◽

Axial Muscle ◽

Weight Support ◽

Cord Injury

Giszter, Simon, William Kargo, Michelle Davies, and Motohide Shibayama. Fetal transplants rescue axial muscle representations in M1 cortex of neonatally transected rats that develop weight support. J. Neurophysiol. 80: 3021–3030, 1998. Intraspinal transplants of fetal spinal tissue partly alleviate motor deficits caused by spinal cord injury. How transplants modify body representation and muscle recruitment by motor cortex is currently largely unknown. We compared electromyographic responses from motor cortex stimulation in normal adult rats, adult rats that received complete spinal cord transection at the T8–T10 segmental level as neonates (TX rats), and similarly transected rats receiving transplants of embryonic spinal cord (TP rats). Rats were also compared among treatments for level of weight support and motor performance. Sixty percent of TP rats showed unassisted weight-supported locomotion as adults, whereas ∼30% of TX rats with no intervention showed unassisted weight-supported locomotion. In the weight-supporting animals we found that the transplants enabled motor responses to be evoked by microstimulation of areas of motor cortex that normally represent the lumbar axial muscles in rats. These same regions were silent in all TX rats with transections but no transplants, even those exhibiting locomotion with weight support. In weight-supporting TX rats low axial muscles could be recruited from the rostral cortical axial representation, which normally represents the neck and upper trunk. No operated animal, even those with well-integrated transplants and good weight-supported locomotion, had a hindlimb motor representation in cortex. The data demonstrate that spinal transplants allow the development of some functional interactions between areas of motor cortex and spinal cord that are not available to the rat lacking the intervention. The data also suggest that operated rats that achieve weight support may primarily use the axial muscles to steer the pelvis and hindlimbs indirectly rather than use explicit hindlimb control during weight-supported locomotion.

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Dynamic organization of primary motor cortex output to target muscles in adult rats I. Long-term patterns of reorganization following motor or mixed peripheral nerve lesions

Experimental Brain Research ◽

10.1007/bf00229318 ◽

1990 ◽

Vol 79 (3) ◽

Cited By ~ 195

Author(s):

J.N. Sanes ◽

S. Suner ◽

J.P. Donoghue

Keyword(s):

Motor Cortex ◽

Peripheral Nerve ◽

Primary Motor Cortex ◽

Adult Rats ◽

Nerve Lesions ◽

Peripheral Nerve Lesions ◽

Dynamic Organization

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Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries

European Journal of Neuroscience ◽

10.1111/ejn.12218 ◽

2013 ◽

Vol 38 (2) ◽

pp. 2271-2279 ◽

Cited By ~ 9

Author(s):

Shashank Tandon ◽

Niranjan Kambi ◽

Hisham Mohammed ◽

Neeraj Jain

Keyword(s):

Spinal Cord ◽

Motor Cortex ◽

Spinal Cord Injuries ◽

Adult Rats

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INNV-01. NEUROLOGIC IMPROVEMENT WITH CORTICOSTEROIDS PRIOR TO SURGERY IS PREDICTIVE OF DURABLE POST-OPERATIVE IMPROVEMENT IN MOTOR DEFICITS DUE TO BRAIN METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.485 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii116-ii116

Author(s):

Stephen Bowden ◽

Barry Cheaney ◽

Nasser Yaghi ◽

Daniel Munger ◽

Christian Lopez Ramos ◽

...

Keyword(s):

Brain Metastases ◽

Clinical Characteristics ◽

Mass Effect ◽

Motor Dysfunction ◽

Motor Deficits ◽

Chi Square ◽

Sustained Improvement ◽

Neurologic Function

Abstract Corticosteroids reduce vasogenic cerebral edema and are thought to improve related neurologic deficits or symptoms of increased intracranial pressure. Brain metastases are typically associated with a large amount of edema and, consequently, come with a disproportionate degree of mass effect that may cause such deficits. There remains no standard approach to pre-operative corticosteroid therapy, nor is it understood what clinical characteristics are associated with a neurologic response to pre-operative steroids. We examined characteristics of steroid responders versus non-responders and, further, evaluated whether a response to preoperative steroids is predictive of durable improvement in neurologic function. Patients with pathology-proven brain metastases who underwent open surgical resection between 2009 and 2019 were identified from departmental records. Charts were reviewed to identify patients with motor dysfunction who received corticosteroids prior to surgery. Multiple patient and clinical characteristics were extracted and compared using student t-, chi-square, and Fisher’s exact tests. 90 patients exhibited pre-operative motor deficits, 69 of whom received corticosteroids prior to surgery (dose 2 – 112 mg; median 25 mg). 34 patients neurologic function improved prior to surgery, whereas 35 patients had no demonstrable improvement. All 34 patients (100%) whose motor function improved pre-operatively with steroids had sustained improvement at follow-up, whereas 27 of 35 (77%) patients who did not improve pre-operatively were better at follow-up (p = 0.005). All other clinical characteristics were similar between responders and non-responders. All motor deficits related to brain metastases that responded to steroids prior to surgery demonstrated durable improvement at follow-up, suggesting such an improvement portends a favorable long-term functional outcome. Conversely, a failure to improve with steroid therapy confers a more guarded prognosis.

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Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome

10.1101/2021.07.05.451143 ◽

2021 ◽

Author(s):

Jing Wang ◽

Henning Froehlich ◽

Felipe Bodaleo Torres ◽

Rangel Leal Silva ◽

Amit Agarwal ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Language Impairment ◽

Motor Coordination ◽

Neurodevelopmental Disorder ◽

Motor Impairment ◽

Motor Dysfunction ◽

Motor Deficits ◽

Cytochrome C Release ◽

And Oxidative Stress

There is increasing evidence that mitochondrial homeostasis - influenced by both genetic and environmental factors - is crucial in neurodevelopment. FOXP1 syndrome is a neurodevelopmental disorder that manifests motor dysfunction, intellectual disability, autism and language impairment. In this study, we used a Foxp1+/- mouse model to address whether cognitive and motor deficits in FOXP1 syndrome are associated with mitochondrial dysfunction and oxidative stress. Here we show that genes with a role in mitochondrial biogenesis and dynamics (e.g. Foxo1, Pgc-1α, Tfam, Opa1, and Drp1) were dysregulated in the striatum of Foxp1+/- mice at different postnatal stages. Furthermore, in the striatum of Foxp1+/- animals, mitochondrial membrane potential was disrupted, and reactive oxygen species, lipid peroxidation and cytochrome c release were significantly elevated. These features can explain the reduced neurite branching, learning and memory, endurance, and motor coordination that we observed in these animals. Taken together, we provide strong evidence of mitochondrial dysfunction in Foxp1+/- mice, suggesting that insufficient energy supply and excessive oxidative stress underlies the cognitive and motor impairment in FOXP1 deficiency.

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The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

BioMed Research International ◽

10.1155/2017/5125980 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

António Nogueira ◽

Francisco Peixoto ◽

Maria Manuel Oliveira ◽

Carlos André Pires ◽

Bruno Colaço ◽

...

Keyword(s):

Oxidative Stress ◽

Renal Function ◽

Renal Mass ◽

Wistar Rats ◽

Reduced Glutathione ◽

Mass Reduction ◽

Significant Difference ◽

Male Wistar Rats ◽

And Oxidative Stress

Purpose.This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction.Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment(n=14); RMR + CAA: RMR rats treated with CAA(n=13); SO: SO rats without treatment(n=13); and SO + CAA: SO rats treated with CAA(n=13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months.Results.RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity(p<0.05)and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity(p<0.05)and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function.Conclusions.These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.

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Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0030 ◽

2015 ◽

Vol 93 (6) ◽

pp. 548-557 ◽

Cited By ~ 21

Author(s):

Gabriela Kozuchovski Ferreira ◽

Eria Cardoso ◽

Francieli Silva Vuolo ◽

Monique Michels ◽

Elton Torres Zanoni ◽

...

Keyword(s):

Oxidative Stress ◽

Gold Nanoparticles ◽

Energy Metabolism ◽

Acute Administration ◽

Sod Activity ◽

Adult Rats ◽

Protein Levels ◽

Carbonyl Protein ◽

Term Administration

This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

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