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

Abstract

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.

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

“…In the last years, we have shown that xenobiotics such as mercury, lead, and fluoride, have an interesting ability to modulate the proteostasis system [ 52 , 53 , 66 , 67 ]. One complex involved in proteostasis is the ubiquitin-proteasome, which regulates the degradation of proteins, along with the Heat Shock Proteins (HSP), which also work on the degradation process, but have special functions in preventing the misfolding of proteins that could lead to the formation of protein aggregates [ 68 , 69 ].…”

“…The proteomic data analyses were only possible due to the comparability between the samples within the same group, and the use of Protein Lynx GlobalSERVER software, robust software for data analyses, was able to determine the p values, hence the quantitative proteomic analysis, considering p < 0.05 for downregulated proteins and 1 − p > 0.95 for upregulated proteins. Detailed methodology is available elsewhere [ 11 , 66 , 86 ].…”

Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum

“…Previous studies have shown that Pb is a neurotoxicant that can cause impaired motor function, behavioral dysfunction, and cognitive decline in humans and rats (5)(6)(7). Chronic exposure to Cd is associated with various adverse effects including memory loss, motor neuron disease, behavioral changes, delayed psychomotor activity in workers (8)(9)(10), and impaired memory and learning in experimental animals (11).…”