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Manganese Neurotoxicity

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Handbook of Neurotoxicity

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Abstract

Manganese (Mn) is one of the most abundant naturally occurring elements in the Earth’s crust. It is essential for many living organisms but also has been broadly used in industry due to its chemical properties. Because of this wide usage, Mn has become an important environmental toxin. Since this metal has been associated to a parkinsonian-like syndrome called manganism, it has been extensively studied, with a major focus on its effects on neuronal cells. The research on Mn absorption, distribution, biological effects, and reliable biomarkers has been extensive; however, much has not been uncovered yet, and new findings have been continuously added to the literature. Several animal models have been contributing to this field, providing genetic, epigenetic, molecular, biochemical, and physiological basis for the whole understanding of neurotoxicity induced by Mn. This chapter will cover up-to-date data on kinetics and neurotoxic mechanisms and how different animal models have contributed to the knowledge on Mn-induced neurotoxicity.

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Abbreviations

DAT:

Dopamine transporters

NAD:

Nicotinamide adenine dinucleotide

ADHD:

Attention-deficit/hyperactivity disorder

ASK-1:

Apoptosis signal-regulating kinase1

ATF4:

Activating transcription factor 4

ATP:

Adenosine triphosphate

BBB:

Blood-brain barrier

Bcl-2:

B-cell lymphoma 2

Ca:

Calcium

CNS:

Central nervous system

Cu:

Copper

Cyt C:

Cytochrome c

DA:

Dopamine

DAT:

Dopamine transporter

DCT:

Divalent cation transporter

DMT1/NRAMP2:

Natural resistance-associated macrophage protein 2

DNA:

Deoxyribonucleic acid

eIF2α:

Eukaryotic initiation factor 2 alpha

ERK:

Extracellular signal-regulated kinase

FDOPA:

6-[(18)F]fluoro-l-dopa

Fe:

Iron

GABA:

Gamma-aminobutyric acid

GFP:

Green fluorescent protein

GI:

Gastrointestinal

GPCR:

G-protein-coupled receptors

HMGB1:

High mobility group protein B1

HSP:

Heat shock protein

IPD:

Idiopathic Parkinson’s disease

IRE1:

Serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1

JNK:

Jun N-terminal kinase

L-DOPA:

Levodopa

LRRK2:

Leucine-rich repeat kinase 2

MCT:

Mn-citrate transporters 

Mg:

Magnesium

MMT:

Methylcyclopentadienyl manganese tricarbonyl

Mn:

Manganese

MPTP:

Mitochondrial permeability transition pore

MRI:

Magnetic resonance imaging

NF-kB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PC-12:

Pheochromocytoma cell line

PD:

Parkinson’s disease

PERK:

Protein kinase RNA-like endoplasmic reticulum kinase

PET:

Positron emission tomography

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SH-SY5Y:

Neuroblastoma cell line

SLC:

Solute carrier family

SPCA:

Secretory pathway Ca2+ ATPase

Tf:

Transferrin

TFEB:

Transcription factor EB

TH:

Tyrosine hydroxylase

TPN:

Total parenteral nutrition

VMAT2:

Vesicular monoamine transporter type 2

Xbp1:

X-box binding protein 1

ZIP:

Zrt- and Irt-like proteins

Zn:

Zinc

Δψm:

Inner membrane potential

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Acknowledgments

Authors are thankful to the funding grants NIH R01ES07331 and R01ES10563 (MA, ABB), INCT-EN, CAPES, CNPq, and FAPERGS (DSA and JBTR).

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Authors and Affiliations

  1. Universidade Federal do Pampa, Uruguaiana, Brazil

    Daiana Silva Ávila

  2. Universidade Federal de Santa Maria, Santa Maria, Brazil

    João Batista Teixeira Rocha

  3. Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA

    Yousef Tizabi

  4. I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Ana Paula Marreilha dos Santos

  5. Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A, Mexico City, Mexico

    Abel Santamaría

  6. School of Health Sciences, Purdue University, West Lafayette, IN, USA

    Aaron B. Bowman

  7. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA

    Michael Aschner

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  1. Daiana Silva Ávila
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  2. João Batista Teixeira Rocha
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  3. Yousef Tizabi
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  4. Ana Paula Marreilha dos Santos
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  5. Abel Santamaría
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  6. Aaron B. Bowman
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  7. Michael Aschner
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Correspondence to Michael Aschner .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Ávila, D.S. et al. (2021). Manganese Neurotoxicity. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_3-1

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