Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular Mechanisms of Lead Neurotoxicity

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 19610

Share This Special Issue

Special Issue Editors

Prof. Dr. Dariusz Chlubek

E-Mail Website
Guest Editor

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70111 Szczecin, Poland
Interests: metabolism of trace elements; toxic elements; ecotoxicology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Irena Baranowska-Bosiacka

E-Mail Website
Guest Editor

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland
Interests: metallomics; neurotoxicology; neurobiochemistry and molecular biology of heavy metals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the introduction of numerous preventative measures that have helped to reduce the use of lead in industry and other areas of life, its presence in the environment and toxicity rank it second among the most dangerous environmental poisons (Substance Priority List, 2018, ATSDR). Its neurotoxic effects are especially pronounced in a developing brain, and exposure in prenatal and early postnatal periods causes numerous metabolic and structural changes, resulting in neurobehavioural and cognitive disorders.

Various papers show a correlation between elevated blood levels of lead in children and impaired memory, concentration, learning, and reduced IQ levels. Recent studies also suggest the significant role of lead in the pathogenesis of neurodevelopmental disorders such as autism, schizophrenia, and ADHD. Furthermore, neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease are likely to be the result not only of genetic and lifestyle factors but also of early life exposure to environmental risk factors such as lead. Although the precise mechanisms of lead neurotoxicity have not been fully described, some researchers indicate its negative influence at electrophysiological, neurobiochemical, and molecular levels.

Given the above, we would like to encourage researchers to send original papers and reviews identifying and explaining the mechanisms of the neurotoxic activity of lead, with particular emphasis on the influence of this element on neurogenesis, signal transmission pathways, synaptic protein function, synaptic transmission and plasticity, the induction and propagation of inflammation, and on astrocyte-neuron metabolic cooperation, i.e., all molecular mechanisms responsible for potential cognitive impairment and intensification of neurodegenerative processes in exposure to lead.

Prof. Dariusz Chlubek
Prof. Irena Baranowska-Bosiacka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Lead-induced neurodegeneration
Lead-induced neuroinflammation
Developmental lead neurotoxicity
Lead neurobehavioral and cognitive dysfunction mechanisms
Lead neurotoxicity in in vitro studies

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

18 pages, 2308 KiB

Open AccessArticle

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

by Ana Carolina Alves Oliveira, Aline Dionizio, Francisco Bruno Teixeira, Leonardo Oliveira Bittencourt, Giza Hellen Nonato Miranda, Géssica Oliveira Lopes, Everton L. P. Varela, Mariane Nabiça, Paula Ribera, Kelly Dantas, Aline Leite, Marília Afonso Rabelo Buzalaf, Marta Chagas Monteiro, Cristiane Socorro Ferraz Maia and Rafael Rodrigues Lima

Int. J. Mol. Sci. 2020, 21(18), 6937; https://doi.org/10.3390/ijms21186937 - 21 Sep 2020

Cited by 11 | Viewed by 2371

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. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Lead Neurotoxicity)

► Show Figures

Graphical abstract

20 pages, 5458 KiB

Open AccessArticle

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

by Luana Ketlen Reis Leão, Leonardo Oliveira Bittencourt, Ana Carolina Oliveira, Priscila Cunha Nascimento, Giza Hellen Nonato Miranda, Railson Oliveira Ferreira, Mariane Nabiça, Kelly Dantas, Aline Dionizio, Sabrina Cartágenes, Marília Afonso Rabelo Buzalaf, Maria Elena Crespo-Lopez, Cristiane S F Maia and Rafael Rodrigues Lima

Int. J. Mol. Sci. 2020, 21(10), 3571; https://doi.org/10.3390/ijms21103571 - 18 May 2020

Cited by 18 | Viewed by 2751

Abstract

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. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Lead Neurotoxicity)

► Show Figures

Graphical abstract

14 pages, 3002 KiB

Open AccessArticle

Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages

by Emilia Metryka, Patrycja Kupnicka, Patrycja Kapczuk, Donata Simińska, Maciej Tarnowski, Marta Goschorska, Izabela Gutowska, Dariusz Chlubek and Irena Baranowska-Bosiacka

Int. J. Mol. Sci. 2020, 21(6), 2254; https://doi.org/10.3390/ijms21062254 - 24 Mar 2020

Cited by 9 | Viewed by 3092

Abstract

The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 μg/dL and 10 μg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Lead Neurotoxicity)

► Show Figures

Graphical abstract

20 pages, 4325 KiB

Open AccessArticle

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

by Ngoc Hieu Bui Thi, Ngoc Anh Nguyen Thi, Gilbert Audira, Petrus Siregar, Sung-Tzu Liang, Jong-Chin Huang and Chung-Der Hsiao

Int. J. Mol. Sci. 2020, 21(5), 1844; https://doi.org/10.3390/ijms21051844 - 07 Mar 2020

Cited by 34 | Viewed by 5170

Abstract

Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl₂ for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl₂ at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl₂-exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Lead Neurotoxicity)

► Show Figures

Figure 1

19 pages, 1689 KiB

Open AccessArticle

Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

by Karina Chibowska, Jan Korbecki, Izabela Gutowska, Emilia Metryka, Maciej Tarnowski, Marta Goschorska, Katarzyna Barczak, Dariusz Chlubek and Irena Baranowska-Bosiacka

Int. J. Mol. Sci. 2020, 21(3), 1083; https://doi.org/10.3390/ijms21031083 - 06 Feb 2020

Cited by 39 | Viewed by 5414

Abstract

Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Lead Neurotoxicity)

► Show Figures

Journal Menu

Journal Browser

Molecular Mechanisms of Lead Neurotoxicity

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI