Neurons and the DHA Principle

Neurons and the DHA Principle

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Features

  • Explores the role of DHA in the human brain and the molecular biology of DHA in neurons
  • Includes extensive data showing the essential roles of DHA in neuron biochemistry
  • Highlights sophisticated mechanisms that have evolved to protect DHA against oxidative damage
  • Emphasizes how the benefits of DHA in neurons are balanced against risks, especially neurodegeneration
  • Includes case histories of neurodegeneration and age-dependent diseases to illustrate the duality of DHA in brain health and decline in the era of human longevity

Summary

Studies with bacteria and other systems suggest that the omega-3 fatty acid DHA confers great benefits to neurons in maximizing both speed of neural impulses and energy efficiency. Unfortunately, studies also show that DHA’s ease of oxidation damages membrane integrity. Exploring this duality, Neurons and the DHA Principle proposes a new model for the causes of neurodegeneration, in which DHA-enriched membranes of neurons become dysfunctional and energetically wasteful, triggering the premature death of neurons.

The challenge of this book is to digest how DHA acts as an essential building block of neurons while also conspiring for their assassination during aging. As the book reviews the extraordinary properties of DHA in life forms from deep-sea bacteria to human neurons, it asks:

  • Is there a trade-off between speed and efficiency of brain function enabled by DHA versus longevity or life span?
  • Has modern medicine advanced significantly in the treatment of the body but not necessarily of the brain?
  • What are the molecular explanations for the decline in brain health during the age of longevity?

A full accounting of the roles of DHA in neurons requires balancing the enormous benefits of these molecules against the risks. Introducing the dual chemical personalities of DHA from an evolutionary perspective, Neurons and the DHA Principle explores DHA from the standpoint of benefit–risk analysis, opening new perspectives for understanding how DHA functions in neurons.

Table of Contents

Section I Evolution and Essential Roles of DHA in Neurons
Nature of Neurons and Their Specialized Membranes
Some Brain Statistics
A Clean, Constant, and Protective Environment Allows Neurons to Perform at Maximum Efficiencies
Microglia Destroy Pathogens and Scavenge Cellular Debris But Have a Dangerous Side
Our Brain Computer Is an Oily Computer
Neurons Have Evolved DHA-Enriched Membranes That Play Essential Roles
The Brain as a Machine
Protecting DHA Membranes of Neurons Is One of the Secrets to the Health and Longevity of the Brain
References

DHA Contributes Both Benefits and Risks to Mammals
Fertility
Vision
Healthy Heart
Cancer-Free Colon
Risks of DHA Including Vision Impairment
References

Use It or Lose It Concept of Brain Health Is Linked to DHA
Use It or Lose It Mechanism of Brain Development is a Marvel of Nature
How Many Neurons to Make a Birdsong?
Lifelong Learning Requires Synaptic Plasticity and Selective Axon Growth
Membrane Exocytosis/Endocytosis as a Means to Modulate Synaptic Strength
DHA as a Momentary Memory Molecule?
References

Evolution and DHA: Redefining the DHA Principle
DHA Maximizes Energy Efficiency in Human Neurons
DHA Likely Came from the Sea
Darwinian Selection of the Fittest Oils for Neurons of Different Animals
DHA Membranes in Our Brain Result from a Delicate Evolutionary Balancing Act
DHA Does Not Work Alone and Is Blended with Cholesterol and Other Lipid Structures to Maintain Energy-Efficient Neuronal Membranes
DHA Plays an Essential Role in Membrane Growth, Development, and Efficiency
Energy Limitation of an Island Environment Might Have Selected the Tiny, Yet Homo sapiens–Like Brain of Hobbit (Homo floresiensis)
References

Section II Benefits of DHA
DHA Is "King Omega" for Maximizing Mental Speed
DHA’s Twisty Tail Speeds Sensory and Mental Processes
Sensory Perception Depends on Extreme Membrane Motion Contributed by DHA
Membrane Asymmetry Enabling Leaflet-Specific Motion Is Important in Neurons
DHA Speeds Up Rates of Cycling of Synaptic Vesicles Important in Fast-Firing Neurons
References

DHA Improves Energy Efficiency in Neurons
A Significant Amount of Brain Energy Is Used to Maintain Neurons Ready to Fire Day and Night
Tiny Synaptic Vesicles Show How Energy Efficiency in DHA-Enriched Membranes Is Improved by Using Cholesterol to Plug Proton Leaks
"Use It or Waste It" Concept of Brain Energy Efficiency
Myelination Also Increases Speed and Energy Efficiency
Why Is DHA Favored over EPA in Human Neurons?
References

Wild Conformational Dynamics of DHA Might Save Energy by Sealing Stretch-Induced Defects as Fast as They Occur in Membranes
Mechanical Stress Model of Sperm Tails
Dynamic Space-Filling Conformations of DHA
Axon Membranes Are Subject to Stretching during Normal Growth and during Brain Trauma
Turgor (Osmotic Pressure) Is Likely Required for Stretch Growth of Axons
Stretch-Induced Defects Likely Occur in Membranes of Cilia, Red Blood Cells, and Heart Muscle Cells
References

Section III: Risks of DHA
Lipid Whisker Model and Water-Wire Theory of Energy Uncoupling in Neurons
Lipid Whisker Model Applied to Neurons
Oxidatively Truncated Phospholipids Act Directly as Signaling Molecules for Activating Phagocytosis
Lipid Whiskers Might Generate Energy-Uncoupling Water-Wires
References

Neurons Boost Their Energy State by Using Powerful Antioxidant Systems to Protect Their Membranes against Damage
The Brain Hoards High Levels of Vitamin C: Case History of Scurvy
Mechanisms for Concentrating Ascorbate in Neurons Are Known in Detail
Brief Chemistry of Ascorbate as an Antioxidant
Vitamin E, a Membrane-Based Antioxidant, Works Synergistically with Vitamin C to Protect Neural Membranes
References

Oxygen-Dependent Damage (Lipid Peroxidation) of DHA Membranes of Neurons Is Inevitable and Requires Novel Mechanisms for Long-Term Protection
Rapid Turnover of Rhodopsin Disks
Rhodopsin and Other Proteins Are Targets of Oxidative Damage
Sperm Tail Membranes as Surrogates for Axons
Slow Turnover of DHA in the Brain Was Not Expected
Sifting through the Lipofuscin "Garbage Pile" for Clues to Neuron Aging
Sequestration of Metals Known to Promote DHA Oxidation Is Vital for Neuron Health
Hypothesis Number 1: Myelin Forms a Protective Shield against Oxidative Damage to Axons
Hypothesis Number 2: Taurine as an Antioxidant
Hypothesis Number 3: Melatonin as an Antioxidant
References

Section IV Revised Membrane Pacemaker Theory of Aging and Age-dependent Diseases
Revised Mitochondrial Theory of Aging and Brain Span
Nature of Mitochondria as Powerhouses for the Cell
Mitochondrial DNA Is a Circular Miniature Chromosome Encoding 37 Genes Essential for Energy Production
Data Derived from Mutator Mice Have Led to a New Theory of Aging in Which Energy Stress Replaces Oxidative Stress as the Primary Cause of Aging
Humans with Mutator Genes Display Symptoms of Premature Neurodegeneration before Symptoms of Aging
Selective Targeting of DHA Away from Mitochondrial Membranes as a Secret to a Long Human Brain Span
References

Development of Dual Energy Pacemaker Theory of Aging: Role of the Membrane
Energy Uncoupling and the Importance of the Membrane as Critical Gatekeeper for Conserving or Wasting Energy
Insects Dramatically Increase Life Span by Dietary Manipulation and Optimal Tuning of Polyunsaturated Fatty Acid Synthesis
First Lesson from Hummingbirds: DHA Turbocharges Mitochondria
Second Lesson from Hummingbirds: The Hardest Working Mitochondria Wear Out Fastest
Third Lesson from Hummingbirds: "Energy-Stressed" Mitochondria Accumulate Mutations Faster
Lessons from Small Mammals: Less DHA, Longer Life Span
Membrane Pacemaker Model Is Consistent with the Bowhead Whale as Longest Lived Mammal
References

Membranes and Cancer
Retinoblastoma Occurs in a Tissue with the Highest Levels of DHA in the Body
Heavy Trafficking of DHA within the Developing Brain Might Potentiate Brain Tumors in Children
DHA Is a Major Building Block for Sperm Membranes: Is There an Increased Risk of Cancer in the Testes?
Correlation between High Levels of DHA in Blood and Aggressive Prostate Cancer
Chemotherapy Patients Are Advised Not to Take Fish Oil Supplements
Asymmetrical Phospholipids as Possible Promoters of Breast Cancer
Does Generalized Cellular Energy Deficiency Govern Rates of Cancer-Causing Nuclear Mutations?
References

Section V DHA Links Aging and Neurodegeneration
Parkinson’s Disease
Parkinsonian Chemicals Likely Act by Accelerating Energy-Oxidative Stresses via a Chain Reaction Mechanism
MPTP: A Potent Neurotoxin
A Closer Look at MPTP as a Mitochondrial Energy Poison versus an Oxidative Threat
Parkinsonian Neurons Are Likely Predisposed to Energy Stress Making Them Extremely Sensitive to Chemicals in the Environment
Neurotoxic Damage to Parkinsonian Neurons May Recruit Hyperactive Microglia Causing More Damage
Mitochondrial Mutations as a Genetic Pacemaker for Age-Dependent Parkinson’s
Dual Energy-Pacemaker Model of Age-Dependent Parkinson’s Disease
References

Prion Diseases
A Spongy-Brain Disease in the Highlands of New Guinea
Prion Replication Is an Amazing Process and Depends on Dysfunctional Protein Processing
Does Energy Play a Role in How Prions Pick Their First Neuron Target?
Prion-Infected Neurons Might Be Subjected to Membrane Energy Uncoupling Caused by the Prion
Numerous Pinpoint Brain Lesions Caused by Prions May Spread as the Result of Microglial-Mediated Neuron Damage
A Protective Gene against Kuru Found in Survivors of New Guinea Epidemic
References

Brain Trauma–Induced Dementia
High Rates of Brain Trauma in Sports and Combat
Axon Stretch Model of Trauma-Triggered Alzheimer’s
Inflammation Model
Suicide Peptide Model
Energy Stress Caused by DHA Might Link the Three Models
References

Alzheimer’s Disease
An Individual Energy-Stressed or Damaged Neuron Might Generate a Focal Point for Alzheimer’s
Spreading from a Focal Point Might Be Caused by an Inflammatory Cascade Linking DHA and Alzheimer’s Disease
Blocking Neuron Death in a Mouse Model of Alzheimer’s Disease by Knockout of a Key Signaling Receptor on Microglia
Is the Toxic Peptide Tau the Long-Awaited Infective Agent Causing the Spread of Alzheimer’s Disease?
DHA Oxidation Products in Cerebrospinal Fluid Help Validate the DHA Principle
Demyelination Occurring during Aging Might Expose DHA-Enriched Membranes of Axons of White Matter to Lipid Peroxidation
Neuron Membranes Seem to Require Extraordinary Protection: The FOXO Story
Effect of Insulin on Symptoms of Alzheimer’s Disease
Working Model of Alzheimer’s as a Membrane Disease
References

Author Bio(s)

Raymond C. Valentine is a Visiting Scholar at University of California, Santa Barbara and Professor Emeritus at the University of California, Davis. David L. Valentine is a Professor of Earth Science at the University of California, Santa Barbara.

 
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