Neurotoxicity of Aluminum

Foreword
Preface
Acknowledgment
Declaration
Contents
Editors and Contributors
Chapter 1: Overview of the Relationship Between Aluminum Exposure and Human Health
1.1 Aluminum in the Environment
1.2 Exposure of Aluminum by Human Beings
1.2.1 Dietary Aluminum Exposure
1.2.1.1 Aluminum in Tea and Cooking Wares
1.2.1.2 Aluminum Exposure From Infant Milk and Formula
1.2.1.3 Aluminum in Other Foods
1.2.1.4 Aluminum in Drinking Water
1.2.2 Aluminum Exposure by Medication and Personal Care Products
1.2.3 Aluminum Exposure by Occupation
1.3 Aluminum Bioavailability and Influencing Factors
1.4 Adverse Effect of Aluminum on Human Beings
1.4.1 Neurotoxic Effects Induced by Occupational Aluminum Exposure
1.4.1.1 Nonneurological Disorders in Occupational Al-Exposed Workers
1.4.1.2 Neurological Disorders in Occupational Al-Exposed Workers
1.4.2 Aluminum Exposure in Drinking Water and Neurological Disorders
1.4.3 Antacid Ingestion and Development of AD
1.4.4 Aluminum-Related ALS and PDT in Specific Regions
1.4.5 Aluminum and Neurodevelopmental Toxicity
1.5 Conclusions
References
Chapter 2: The Chemistry of Human Exposure to Aluminum
References
Chapter 3: Entry and Deposit of Aluminum in the Brain
3.1 Aluminum Enters the Brain
3.1.1 Aluminum Enters the Brain Across the BBB
3.1.1.1 Aluminum Influxes into Brain Across BBB Directly as a Small-Molecular-Weight Pieces
3.1.1.2 Aluminum Entry into Brain Is Mediated by Transferrin (Tf): Transferrin Receptor (TfR), Which Is an Important Iron Carr...
3.1.1.3 Aluminum Citrate Enters into the Brain Mediated by Monocarboxylic Acid Transporters (MCTs), Which Is Additionally a Fa...
3.1.1.4 Aluminum Citrate Enters into the Brain Via System Xc-, Which Is Known to Be a Na+-Independent Glutamate Transporter, a...
3.1.2 Aluminum-Containing Compounds Could Enter into the Brain Through Olfactory Mucosa/Olfactory Bulb Barriers
3.1.3 Little Aluminum Enters the Brain Through Choroid Plexus
3.1.4 Aluminum Enters the Brain Via the Immune System
3.1.4.1 Aluminum-Containing Adjuvants Enter the Brain Via Macrophage Phagocytosis
3.1.4.2 Aluminum Enters the Brain Via Immune Cells Circulating in the Blood and Lymph
3.2 Aluminum Effluxes From the Brain
3.3 The Influence Factors of Aluminum Entry and Depositing in the Brain
3.3.1 Parathyroid Hormone (PTH) and Vitamin D
3.3.2 Permeability of the BBB
3.3.3 Citric Acid
References
Chapter 4: Aluminum as a CNS and Immune System Toxin Across the Life Span
4.1 Introduction: Neurological Diseases and Causality Factors
4.1.1 Aluminum Toxicity: General Considerations for the Impact on Human Neurological Diseases Across the Life Span
4.2 Aluminum in the Biosphere and Forms of Human Exposure
4.2.1 Aluminum Chemistry and the Intersection of Aluminum with the Biosphere
4.2.2 Sources of Aluminum in the Biosphere
4.2.3 Aluminum in Vaccines
4.3 Human and Animal Studies of Aluminum Neurotoxicity
4.3.1 Aluminum-Triggered Genetic Alterations and Protein Expression Levels
4.3.2 miRNA Alterations in Gene Expression
4.4 Overview of Innate Versus Adaptive Immune Systems and Their Roles in CNS Development and Neurological Disease
4.4.1 HPA-Immune System Interactions in Development and Disease
4.4.2 Autoimmunity
4.4.3 Aluminum and Failed Biosemiosis
4.4.4 Aluminum´s Role in Immune System Signaling Errors with a Focus on ASD
4.4.5 Pathogen and Aluminum Activation of the Immune System in Relation to the CNS
4.5 Summary and Final Considerations
References
Chapter 5: Occupational Exposure to Aluminum and Cognitive Impairment
5.1 Introduction
5.2 Exposure Assessment
5.3 Cognitive Impairment
5.4 Conclusion
References
Chapter 6: Exposure to Aluminum in Daily Life and Alzheimer´s Disease
6.1 Introduction
6.2 Natural Sources of Aluminum Exposure
6.3 Anthropogenic Sources of Aluminum Exposure
6.4 Aluminum Exposures of the General Population in Daily Life
6.5 Absorption, Distribution, and Excretion of Aluminum
6.6 Aluminum-Induced Neurotoxicity and Aluminum Hypothesis in the Etiology of AD
6.6.1 Aluminum and Aβ
6.6.2 Aluminum and NFTs
6.6.3 Aluminum and Cell Death
6.6.4 Aluminum and Neuroinflammation
6.7 Epidemiological Evidence of a Relationship Between Aluminum Intake in Daily Life and Alzheimer´s Disease
6.8 Conclusions
References
Chapter 7: Animal Model of Aluminum-Induced Alzheimer´s Disease
7.1 The Involvement of Aluminum in AD
7.2 Aluminum Compounds for the Animal Model
7.2.1 Complex Chemistry of Aluminum
7.2.2 Aluminum Salts and Complexes
7.3 The Aged Rabbits Are More Effective as Animal Models
7.3.1 The Susceptibility of Aged Rabbits in Inducing AD Neuropathology Compared to Young Ones
7.3.2 Al-Induced Neurodegeneration
7.4 Similar Features in Maltolate-Treated Rabbits with AD
7.4.1 Neurofibrillary Degeneration
7.4.2 Oxidative Stress
7.4.3 Apoptosis
7.4.3.1 Mitochondrial Permeability Transition Pores Are Involved in Al-Induced Apoptosis
7.4.3.2 The Endoplasmic Reticulum Plays a Role in Al-Induced Apoptosis
7.5 Animal Models Induced by Nanoaluminum Particles
7.6 Summary
References
Chapter 8: Aluminum-Induced AD-Like Pathological Features
8.1 Introduction
8.2 Abnormal Generation and Deposition of Aβ
8.3 Abnormal Phosphorylation of Tau Protein
8.4 Synaptic Deficits and Neuron Loss
8.5 Conclusions
References
Chapter 9: Aluminum-Induced Neural Cell Death
9.1 Introduction
9.2 Aluminum-Induced Neural Cell Death
9.2.1 Methods
9.2.2 Results
9.2.2.1 Cellular Morphology in Al-Treated Neural Cells
9.2.2.2 Nuclear Morphology in Al-Treated Neural Cells
9.2.2.3 Apoptosis Detection by TUNEL
9.2.2.4 Ultrastructure of Al-Treated Neurons
9.2.2.5 Cell Death Rates Detected by Flow Cytometry
9.2.3 Discussion
9.3 Necroptosis in Aluminum-Induced Neural Cell Death
9.3.1 Methods
9.3.2 Results
9.3.2.1 Morphous and Viability of SH-SY5Y Cells Treated with Al and Nec-1
9.3.2.2 Apoptotic Rate and Necrotic Rate Assay
9.3.2.3 Caspase Activity of Al- and Nec-1-Treated SH-SY5Y Cells
9.3.2.4 LC3 Expression of Al- and Nec-1-Treated SH-SY5Y Cells
9.3.3 Discussion
9.4 Al-Induced Neural Cell Loss and AD
9.4.1 Methods
9.4.2 Results
9.4.2.1 Cell Viability Analysis In Vitro
9.4.2.2 Fluorescence Observation and Analysis of Neural Cell Death Rates In Vitro
9.4.2.3 Western Blot Analysis of the Expression of Cell Death-Related Proteins In Vitro
9.4.2.4 Neural Behavioral Profile in Mice
9.4.2.5 Nec-1 Decreased Neural Cell Death Induced by Al In Vivo
9.4.2.6 Expression of Cell Death-Related Proteins in Cortical Neural Cells In Vivo
9.4.2.7 Expression of AD-Related Proteins in Mice
9.4.2.8 T-Maze Results of Zebrafish Treated with Al plus Nec-1
9.4.2.9 Ach Levels in the Brain Tissues of Al- and/or Nec-1-Treated Zebrafish
9.4.2.10 Nissl Staining in the Brain Tissues of Al- and/or Nec-1-Treated Zebrafish
9.4.2.11 Detection of Necroptosis-Related Marker Genes
9.4.2.12 Immunohistochemical Staining of Apoptosis-Related Proteins
9.4.2.13 Transmission Electron Microscopy
9.4.3 Discussion
9.5 Conclusions
References
Chapter 10: Aluminum-Induced Electrophysiological Variation, Synaptic Plasticity Impairment, and Related Mechanism
10.1 Aluminum Neurotoxicity
10.2 Al-Induced Electrophysiological Variation
10.2.1 Aluminum Effect on Electrical Excitability
10.2.2 Aluminum Effect on Voltage-Operated Ion Channels
10.2.3 Aluminum Effect on Synaptic Plasticity
10.2.4 The Cell Signal Pathways and Aluminum Effect on Synaptic Plasticity
10.2.4.1 Glutamate-NO-cGMP and Aluminum Effect on Synaptic Plasticity
10.2.4.2 PLC Signaling Pathway and Aluminum Effect on Synaptic Plasticity
10.2.4.3 Ca2+-CaM-CaMKII Signaling Pathway and Aluminum Effect
10.2.4.4 The MAPK Pathway and Aluminum Effect on Synaptic Plasticity
10.2.4.5 Wnt Pathway and Aluminum Effect on Synaptic Plasticity
10.3 Conclusion and Future Perspectives
References
Chapter 11: Cross Talk Between Al and Genetic Susceptibility in AD
11.1 Introduction
11.2 Aluminum and AD
11.3 Al and Genetic Susceptibility in AD
11.4 Summary
References
Chapter 12: Epigenetic Modification in Aluminum-Induced Neurotoxicity
12.1 Al May Induce DNA Methylation Changes That May Contribute to AD
12.2 Al May Induce Histone Modification That May Be Involved in AD
12.3 Al Induces Noncoding RNA Regulation in the Nervous System
12.4 Al and Genetic Susceptibility and Epigenetic Modification in AD
12.5 Summary
References
Chapter 13: Neurotoxicity of Aluminum and Its Compound Nanoparticles
13.1 Introduction
13.2 Exposure Routes and Models
13.2.1 Oral Ingestion
13.2.2 Inhalation
13.2.3 Nasal Administration
13.2.4 Injection
13.2.5 Skin Absorption
13.3 Neurotoxicity Induced by Aluminum and Its Compound Nanoparticles
13.3.1 In Vitro Studies
13.3.2 Zebrafish
13.3.3 Invertebrate
13.3.4 Mice
13.3.5 Rats
13.4 Factors Affecting the Neurotoxicity of Aluminum and Its Compound Nanoparticles
13.4.1 Size
13.4.2 Shape
13.4.3 Crystalline Structure
13.4.4 Surface Modification
13.4.5 Others
13.5 Mechanisms Underlying the Neurotoxicity Induced by Aluminum and Its Compound Nanoparticles
13.5.1 Brain-Blood Barrier Damage
13.5.2 Excessive ROS Production
13.5.3 Mitochondrial Damage
13.5.4 Amyloid-β (Aβ) and Tau Protein
13.5.5 Autophagy
13.5.6 Signaling Pathway
13.6 Conclusions and Perspectives
References
Chapter 14: Alumina Nanoparticles Induced Neurotoxic and Neurodevelopmental Toxic Effects
14.1 Introduction
14.2 Neurotoxicity of AlNPs: Toxic Effects of Particle Sizes and Ions
14.2.1 Methods
14.2.2 Result
14.2.2.1 Characterization of Nanoparticles and Dissolve the Determination of Al3+ Content
14.2.2.2 Teratogenic Effects of AlNPs on Zebrafish Larvae
14.2.2.3 Effect of AlNPs on Behavior of Zebrafish
14.2.2.4 Oxidative Stress Level
14.2.2.5 Effect of Different Nanoparticles and Al3+ on Gene Expression
14.2.3 Discussion
14.3 Neurodevelopmental Toxicity of AlNPs
14.3.1 Methods
14.3.2 Result
14.3.2.1 After AlNPs Treatment of Embryos, the Aluminum Content in Adult Zebrafish Brain Increased with Age
14.3.2.2 AlNPs Exposure Reduced Learning and Memory Performance in Adult Zebrafish
14.3.2.3 AlNPs Exposure Changed the Locomotor Activity of Adult Zebrafish Under Dark Conditions
14.3.2.4 AlNPs Exposure Reduced Novel Exploratory Ability of Adult Fish Under Light Conditions
14.3.2.5 AlNPs Exposure Reduced the Expression of Neurotransmitters in the Adult Zebrafish Brain
14.3.2.6 AlNPs Exposure Effect on Zebrafish Brain Oxidative Stress Reaction
14.3.2.7 AlNPs Exposure Reduced the Number of Neurons and Accompanying Autophagy
14.3.3 Discussion
14.4 Exposure of Female Mice to Alumina Nanoparticles During Pregnancy Resulted in Neurodevelopmental Toxicity in Offspring
14.4.1 Methods
14.4.2 Result
14.4.2.1 Female Mice Treated by AlNPs Low Weight Newborn Cub, Seahorse Al Content Is Higher
14.4.2.2 AlNPs-Treated Female Mice Gave Birth to Newborn Pups with Low Physical Value
14.4.2.3 AlNPs-Treated Female Mouse Offspring Showed a Lower Level of Neuromotor Maturation
14.4.2.4 AlNPs-Treated Female Mice Gave Birth to Adolescent Mice That Showed Stronger Anxiety-Like Behavior
14.4.2.5 AlNPs-Treated Female Mice Showed Poor Adolescent Neurobehavioral Performance
14.4.2.6 Adolescent Oxidative Stress Induced by AlNPs-Treated Female Mice
14.4.2.7 Adolescents´ Cerebral Cortex Levels of Neurotransmitters Were Given by Female Mice Treated with AlNPs
14.4.3 Discussion
14.5 The Mitochondrial Autophagy Is Involved in the Neurotoxicity of Damage Caused by Aluminum Oxide Nanoparticles
14.5.1 Methods
14.5.2 Results
14.5.2.1 Effect of AlNPs on the Learning and Memory of Mice
14.5.2.2 AlNPs Treatment of Oxidative Stress in Mice
14.5.2.3 AlNPs Exposure Induced Morphological Changes in the Mitochondria
14.5.2.4 AlNPs Exposure Induced Mitochondrial Function Change
14.5.2.5 AlNPs Protein Related to Cell Death and the Impact of Mitophagy
14.5.2.6 Fluorescence Localization of Mitochondria and Autophagy in Hippocampal Sections
14.5.3 Discussion
References