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Special Issue "Molecular Research in Neurotoxicology 2.0"

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

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Dr. G. Jean Harry
E-Mail Website
Guest Editor
Neurotoxicology Group, NIEHS and National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA
Interests: neurotoxicants; aging; development; inflammation; oxidative stress; signal transduction; hormones; neuropathology; pharmaceuticals; alternative models
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Alterations in nervous system functioning as a result of environmental factors, pharmaceuticals, genetic variability, and health status remain an issue of concern for human health. Recent advancements have been made in our understanding of common biological processes related to neurotoxicity associated with disease states and age-related or genetic vulnerabilities. These advances have been possible due to the ability to examine molecular aspects underlying neurodevelopment, neurodegeneration, and associated processes of neurotoxicity. The integration of this molecular data into the field of neurotoxicology, as it applies to the broad spectrum of environmental exposure now offers a mechanistic framework for understanding the dynamics of neurotoxicity. Further work on epigenetic mechanisms associated with nervous system functioning, e.g., learning and memory, provide additional mechanisms by which regulation of the nervous system can be altered by environmental exposure or by which events occurring during early life stages can influence responses later in life. This topical collection will focus on the integration of established biological processes and molecular events as they relate to the regulation of cellular and functional changes within the nervous system and how this may contribute to neurotoxicity. The collection will include aspects of neurological and neurodegenerative disease, neurodevelopmental disorders, and specific neurotoxicity from environmental or pharmaceutical agents. We are seeking novel research and/or review articles highlighting 1) the variety of molecular signals and integrated networks that underlie adverse responses in the nervous system, 2) how these alterations in molecular signaling translate to alterations in the structure or function of the nervous system (biochemical, physiology, behavior), 3) molecular events occurring during early life that can shift susceptibility in the adult, 4) epigenetic regulatory events as they contribute to neurotoxicity and 5) contributions to life stage events influencing human health.

Dr. G. Jean Harry
Guest Editor

Manuscript Submission Information

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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

  • oxidative stress
  • organophosphorus pesticides
  • neuropathy target esterase (nte)
  • animal models
  • transcription factor signaling
  • cell death
  • receptor mediated events
  • receptor mediated events
  • glia
  • kynurenines
  • quinolinic acid
  • inflammation
  • cytokines
  • heat shock protein 70
  • neurobehavior
  • neuroprotection
  • seizures
  • neurotrophic factors
  • ischemia/hypoxia
  • microglia
  • cyanobacteria
  • heavy metals
  • pharmacological models
  • neurodegeneration
  • ischemia
  • perinatal brain injury
  • neurotoxicants
  • neurodegenerative diseases
  • zinc

Published Papers (5 papers)

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Research

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Article
Nicotine Neurotoxicity Involves Low Wnt1 Signaling in Spinal Locomotor Networks of the Postnatal Rodent Spinal Cord
Int. J. Mol. Sci. 2021, 22(17), 9572; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179572 - 03 Sep 2021
Viewed by 822
Abstract
The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1 µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom [...] Read more.
The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1 µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5–10 µM) on locomotor networks in-vitro. Nicotine 10 µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5–1 µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes indicating a stress response. Excitotoxicity induced by kainate was contrasted by nicotine (10 µM) in the dorsal area and persisted in central and ventral regions with no change in basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology 2.0)
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Article
Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure
Int. J. Mol. Sci. 2021, 22(13), 6662; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136662 - 22 Jun 2021
Viewed by 562
Abstract
Acute liver failure (ALF) is associated with deregulated nitric oxide (NO) signaling in the brain, which is one of the key molecular abnormalities leading to the neuropsychiatric disorder called hepatic encephalopathy (HE). This study focuses on the effect of ALF on the relatively [...] Read more.
Acute liver failure (ALF) is associated with deregulated nitric oxide (NO) signaling in the brain, which is one of the key molecular abnormalities leading to the neuropsychiatric disorder called hepatic encephalopathy (HE). This study focuses on the effect of ALF on the relatively unexplored endothelial NOS isoform (eNOS). The cerebral prefrontal cortices of rats with thioacetamide (TAA)-induced ALF showed decreased eNOS expression, which resulted in an overall reduction of NOS activity. ALF also decreased the content of the NOS cofactor, tetrahydro-L-biopterin (BH4), and evoked eNOS uncoupling (reduction of the eNOS dimer/monomer ratio). The addition of the NO precursor L-arginine in the absence of BH4 potentiated ROS accumulation, whereas nonspecific NOS inhibitor L-NAME or EDTA attenuated ROS increase. The ALF-induced decrease of eNOS content and its uncoupling concurred with, and was likely causally related to, both increased brain content of reactive oxidative species (ROS) and decreased cerebral cortical blood flow (CBF) in the same model. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology 2.0)
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Article
Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice
Int. J. Mol. Sci. 2021, 22(11), 5995; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115995 - 01 Jun 2021
Viewed by 1531
Abstract
Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 [...] Read more.
Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology 2.0)
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Article
A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon, Oncorhynchus keta, Using Mouse Adeno-Associated Viral Vectors
Int. J. Mol. Sci. 2021, 22(11), 5661; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115661 - 26 May 2021
Viewed by 665
Abstract
To date, data on the presence of adenoviral receptors in fish are very limited. In the present work, we used mouse recombinant adeno-associated viral vectors (rAAV) with a calcium indicator of the latest generation GCaMP6m that are usually applied for the dorsal hippocampus [...] Read more.
To date, data on the presence of adenoviral receptors in fish are very limited. In the present work, we used mouse recombinant adeno-associated viral vectors (rAAV) with a calcium indicator of the latest generation GCaMP6m that are usually applied for the dorsal hippocampus of mice but were not previously used for gene delivery into fish brain. The aim of our work was to study the feasibility of transduction of rAAV in the mouse hippocampus into brain cells of juvenile chum salmon and subsequent determination of the phenotype of rAAV-labeled cells by confocal laser scanning microscopy (CLSM). Delivery of the gene in vivo was carried out by intracranial injection of a GCaMP6m-GFP-containing vector directly into the mesencephalic tegmentum region of juvenile (one-year-old) chum salmon, Oncorhynchus keta. AAV incorporation into brain cells of the juvenile chum salmon was assessed at 1 week after a single injection of the vector. AAV expression in various areas of the thalamus, pretectum, posterior-tuberal region, postcommissural region, medial and lateral regions of the tegmentum, and mesencephalic reticular formation of juvenile O. keta was evaluated using CLSM followed by immunohistochemical analysis of the localization of the neuron-specific calcium binding protein HuCD in combination with nuclear staining with DAPI. The results of the analysis showed partial colocalization of cells expressing GCaMP6m-GFP with red fluorescent HuCD protein. Thus, cells of the thalamus, posterior tuberal region, mesencephalic tegmentum, cells of the accessory visual system, mesencephalic reticular formation, hypothalamus, and postcommissural region of the mesencephalon of juvenile chum salmon expressing GCaMP6m-GFP were attributed to the neuron-specific line of chum salmon brain cells, which indicates the ability of hippocampal mammal rAAV to integrate into neurons of the central nervous system of fish with subsequent expression of viral proteins, which obviously indicates the neuronal expression of a mammalian adenoviral receptor homolog by juvenile chum salmon neurons. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology 2.0)
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Review

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Review
Influence of the Aryl Hydrocarbon Receptor Activating Environmental Pollutants on Autism Spectrum Disorder
Int. J. Mol. Sci. 2021, 22(17), 9258; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179258 - 26 Aug 2021
Viewed by 780
Abstract
Autism spectrum disorder (ASD) is an umbrella term that includes many different disorders that affect the development, communication, and behavior of an individual. Prevalence of ASD has risen exponentially in the past couple of decades. ASD has a complex etiology and traditionally recognized [...] Read more.
Autism spectrum disorder (ASD) is an umbrella term that includes many different disorders that affect the development, communication, and behavior of an individual. Prevalence of ASD has risen exponentially in the past couple of decades. ASD has a complex etiology and traditionally recognized risk factors only account for a small percentage of incidence of the disorder. Recent studies have examined factors beyond the conventional risk factors (e.g., environmental pollution). There has been an increase in air pollution since the beginning of industrialization. Most environmental pollutants cause toxicities through activation of several cellular receptors, such as the aryl hydrocarbon receptor (AhR)/cytochrome P450 (CYPs) pathway. There is little research on the involvement of AhR in contributing to ASD. Although a few reviews have discussed and addressed the link between increased prevalence of ASD and exposure to environmental pollutants, the mechanism governing this effect, specifically the role of AhR in ASD development and the molecular mechanisms involved, have not been discussed or reviewed before. This article reviews the state of knowledge regarding the impact of the AhR/CYP pathway modulation upon exposure to environmental pollutants on ASD risk, incidence, and development. It also explores the molecular mechanisms involved, such as epigenesis and polymorphism. In addition, the review explores possible new AhR-mediated mechanisms of several drugs used for treatment of ASD, such as sulforaphane, resveratrol, haloperidol, and metformin. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology 2.0)
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