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

Abstract

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.

Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity

“…The samples of submandibular glands were initially cryofractured with liquid nitrogen and then, two samples from the same group were pooled and all the experiment was proceeded in biological triplicate. The detailed protocol is described in previous publications from our group ( Bittencourt et al, 2019 ; Alves Oliveira et al, 2020 ; Dionizio et al, 2020 ; Leão et al, 2020 ; Lopes et al, 2020 ; Ferreira et al, 2021 ).…”

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

“…Interestingly, it is worthy to point out that in previous proteomic data of hippocampus [ 14 ] after the same lead exposure model, the Apolipoprotein E (P02650, unique in control group) showed the same status of regulation in hippocampus, while Protein S100B (P04631) was up-regulated in motor cortex and down-regulated in hippocampus, on the other hand, these proteins were not changed in cerebellum [ 13 ]. However, the CB1 cannabinoid receptor-interacting protein 1 (Q5M7A7) found up-regulated in this study was exclusively expressed in the control group in cerebellar global proteomic profile.…”

“…This lead administration protocol was based on Gu et al [ 17 ] and reproduced in previous studies from our group [ 12 – 14 , 18 ]. The experimental design is summarized in Figure 1 .…”

“…Recently, we investigated the effects of long-term exposure to lead from adolescence to adulthood on different regions of the Central Nervous System (CNS) [12][13][14]. In the hippocampus, an important region involved in cognitive processes, we observed increased levels of lead, oxidative stress, and altered modulation of proteins related to cell protection, synaptic transmission, associated with intense neuronal loss, and damages to cognitive functions [14]. Our data also showed high levels of lead on spinal cord and cerebellum, and after long-term exposure, a reduction of neurons density in both regions was associated with motor changes [12,13].…”

Effects of Lead Exposure on Blood Electrical Impedance Spectroscopy of Mice

“…Lead is a heavy metal material that has been widely applied in pottery, lead welding, dyes, and cosmetics [1] . Exposure to the high concentration of lead may cause damage to the nervous system, digestive system, blood system, kidney, and other organs [2][3][4] . A new analysis by the Institute for Health Metrics and Evaluation (IHME) has estimated that 815 million children worldwide have a high concentration of lead in their bloodstream [5] .…”