Neurons and the DHA Principle

276 Pages·2012·25.654 MB·English

by  Raymond C. Valentine, David L. Valentine

Neurons
and the
DHA
Principle

Neurons
and the
DHA
Principle
Raymond C. Valentine
David L. Valentine
Boca Raton London New York
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Contents
Preface....................................................................................................................xiii
Acknowledgments.....................................................................................................xv
The.Authors............................................................................................................xvii
Introduction..............................................................................................................xix
Section i evolution and essential Roles of DHA
in neurons
Chapter 1 Nature.of.Neurons.and.Their.Specialized.Membranes.........................3
1.1. Some.Brain.Statistics..................................................................3
1.2. A.Clean,.Constant,.and.Protective.Environment.Allows.
Neurons.to.Perform.at.Maximum.Efficiencies...........................6
1.3. Microglia.Destroy.Pathogens.and.Scavenge.Cellular.
Debris.But.Have.a.Dangerous.Side............................................7
1.4. Our.Brain.Is.an.Oily.Computer..................................................8
1.5. Neurons.Have.Evolved.DHA-.Enriched.Membranes.That.
Play.Essential.Roles....................................................................9
1.6. The.Brain.as.a.Machine............................................................11
1.7. Protecting.DHA.Membranes.of.Neurons.Is.One.of.the.
Secrets.to.the.Health.and.Longevity.of.the.Brain....................13
References...........................................................................................15
Chapter 2 DHA.Contributes.Both.Benefits.and.Risks.to.Mammals...................17
2.1. Fertility.....................................................................................17
2.2. Vision........................................................................................19
2.3. Healthy.Heart...........................................................................20
2.4. Cancer-.Free.Colon....................................................................20
2.5. Risks.of.DHA.Including.Vision.Impairment...........................25
References...........................................................................................26
Chapter 3 Use.It.or.Lose.It.Concept.of.Brain.Health.Is.Linked.to.DHA............29
3.1. Use.It.or.Lose.It.Mechanism.of.Brain.Development.Is.a.
Marvel.of.Nature......................................................................29
3.2. How.Many.Neurons.to.Make.a.Birdsong?...............................32
3.3. Lifelong.Learning.Requires.Synaptic.Plasticity.and.
Selective.Axon.Growth............................................................33
v
vi Contents
3.4. Membrane.Exocytosis/.Endocytosis.as.a.Means.to.
Modulate.Synaptic.Strength.....................................................34
3.5. DHA.as.a.Momentary.Memory.Molecule?..............................34
References...........................................................................................35
Chapter 4 Evolution.and.DHA:.Redefining.the.DHA.Principle..........................37
4.1. DHA.Maximizes.Energy.Efficiency.in.Human.Neurons.........38
4.2. DHA.Likely.Came.from.the.Sea..............................................39
4.3. Darwinian.Selection.of.the.Fittest.Oils.for.Neurons.of.
Different.Animals.....................................................................41
4.4. DHA.Membranes.in.Our.Brain.Result.from.a.Delicate.
Evolutionary.Balancing.Act.....................................................44
4.5. DHA.Does.Not.Work.Alone.and.Is.Blended.with.
Cholesterol.and.Other.Lipid.Structures.to.Maintain.
Energy-.Efficient.Neuronal.Membranes....................................44
4.6. DHA.Plays.an.Essential.Role.in.Membrane.Growth,.
Development,.and.Efficiency....................................................48
4.7. Energy.Limitation.of.an.Island.Environment.Might.
Have.Selected.the.Tiny,.Yet.Homo sapien–Like.Brain.of.
Hobbit.(Homo floresiensis).......................................................50
References...........................................................................................51
Section ii Benefits of DHA
Chapter 5 DHA.Is.“King.Omega”.for.Maximizing.Mental.Speed.....................57
5.1. DHA’s.Twisty.Tail.Speeds.Sensory.and.Mental.Processes......57
5.2. Sensory.Perception.Depends.on.Extreme.Membrane.
Motion.Contributed.by.DHA....................................................60
5.3. Membrane.Asymmetry.Enabling.Leaflet-.Specific.Motion.
Is.Important.in.Neurons...........................................................64
5.4. DHA.Speeds.Up.Rates.of.Cycling.of.Synaptic.Vesicles.
Important.in.Fast-.Firing.Neurons............................................66
References...........................................................................................71
Chapter 6 DHA.Improves.Energy.Efficiency.in.Neurons...................................73
6.1. A.Significant.Amount.of.Brain.Energy.Is.Used.to.
Maintain.Neurons.Ready.to.Fire.Day.and.Night......................73
6.2. Tiny.Synaptic.Vesicles.Show.How.Energy.Efficiency.
in.DHA-.Enriched.Membranes.Is.Improved.by.Using.
Cholesterol.to.Plug.Proton.Leaks.............................................76
Contents vii
6.3. “Use.It.or.Waste.It”.Concept.of.Brain.Energy.Efficiency........80
6.4. Myelination.Also.Increases.Speed.and.Energy.Efficiency......82
6.5. Why.Is.DHA.Favored.over.EPA.in.Human.Neurons?.............82
References...........................................................................................84
Chapter 7 Wild.Conformational.Dynamics.of.DHA.Might.Save.Energy.
by.Sealing.Stretch-.Induced.Defects.as.Fast.as.They.Occur.in.
Membranes..........................................................................................87
7.1. Mechanical.Stress.Model.of.Sperm.Tails.................................87
7.2. Dynamic.Space-.Filling.Conformations.of.DHA.....................91
7.3. Axon.Membranes.Are.Subject.to.Stretching.during.
Normal.Growth.and.during.Brain.Trauma...............................92
7.4. Turgor.(Osmotic.Pressure).Is.Likely.Required.for.Stretch.
Growth.of.Axons......................................................................94
7.5. Stretch-.Induced.Defects.Likely.Occur.in.Membranes.of.
Cilia,.Red.Blood.Cells,.and.Heart.Muscle.Cells......................95
References...........................................................................................97
Section iii R isks of DHA
Chapter 8 Lipid.Whisker.Model.and.Water-.Wire.Theory.of.Energy.
Uncoupling.in.Neurons.....................................................................101
8.1. Lipid.Whisker.Model.Applied.to.Neurons.............................102
8.2. Oxidatively.Truncated.Phospholipids.Act.Directly.as.
Signaling.Molecules.for.Activating.Phagocytosis..................104
8.3. Lipid.Whiskers.Might.Generate.Energy-.Uncoupling.
Water-.Wires............................................................................105
References.........................................................................................109
Chapter 9 Neurons.Boost.Their.Energy.State.by.Using.Powerful.Antioxidant.
Systems.to.Protect.Their.Membranes.against.Damage.....................111
9.1. The.Brain.Hoards.High.Levels.of.Vitamin.C:.Case.
History.of.Scurvy...................................................................112
9.2. Mechanisms.for.Concentrating.Ascorbate.in.Neurons.
Are.Known.in.Detail..............................................................112
9.3. Brief.Chemistry.of.Ascorbate.as.an.Antioxidant...................113
9.4. Vitamin.E,.a.Membrane-.Based.Antioxidant,.Works.
Synergistically.with.Vitamin.C.to.Protect.Neural.
Membranes.............................................................................115
References.........................................................................................117
viii Contents
Chapter 10 Oxygen-.Dependent.Damage.(Lipid.Peroxidation).of.DHA.
Membranes.of.Neurons.Is.Inevitable.and.Requires.Novel.
Mechanisms.for.Long-.Term.Protection.............................................119
10.1. Rapid.Turnover.of.Rhodopsin.Disks......................................120
10.2. Rhodopsin.and.Other.Proteins.Are.Targets.of.Oxidative.
Damage...................................................................................122
10.3. Sperm.Tail.Membranes.as.Surrogates.for.Axons...................123
10.4. Slow.Turnover.of.DHA.in.the.Brain.Was.Not.Expected........125
10.5. Sifting.through.the.Lipofuscin.“Garbage.Pile”.for.Clues.
to.Neuron.Aging.....................................................................126
10.6. Sequestration.of.Metals.Known.to.Promote.DHA.
Oxidation.Is.Vital.for.Neuron.Health.....................................127
10.7. Hypothesis.Number.1:.Myelin.Forms.a.Protective.Shield.
against.Oxidative.Damage.to.Axons......................................129
10.8. Hypothesis.Number.2:.Taurine.as.an.Antioxidant.................130
10.9. Hypothesis.Number.3:.Melatonin.as.an.Antioxidant.............132
References.........................................................................................133
Section iV Revised Membrane Pacemaker theory
of Aging and Age- Dependent Diseases
Chapter 11 Revised.Mitochondrial.Theory.of.Aging.and.Brain.Span................137
11.1. Nature.of.Mitochondria.as.Powerhouses.for.the.Cell.............137
11.2. Mitochondrial.DNA.Is.a.Circular.Miniature.Chromosome.
Encoding.37.Genes.Essential.for.Energy.Production............140
11.3. 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...................142
11.4. Humans.with.Mutator.Genes.Display.Symptoms.of.
Premature.Neurodegeneration.before.Symptoms.of.Aging....143
11.5. Selective.Targeting.of.DHA.Away.from.Mitochondrial.
Membranes.as.a.Secret.to.a.Long.Human.Brain.Span...........144
References.........................................................................................149
Chapter 12 Development.of.Dual.Energy.Pacemaker.Theory.of.Aging:.Role.
of.the.Membrane...............................................................................151
12.1. Energy.Uncoupling.and.the.Importance.of.the.Membrane.
as.Critical.Gatekeeper.for.Conserving.or.Wasting.Energy....152
12.2. Insects.Dramatically.Increase.Life.Span.by.Dietary.
Manipulation.and.Optimal.Tuning.of.Polyunsaturated.
Fatty.Acid.Synthesis...............................................................154
Contents ix
12.3. First.Lesson.from.Hummingbirds:.DHA.Turbocharges.
Mitochondria..........................................................................156
12.4. Second.Lesson.from.Hummingbirds:.The.Hardest.
Working.Mitochondria.Wear.Out.Fastest...............................157
12.5. Third.Lesson.from.Hummingbirds:.“Energy-.Stressed”.
Mitochondria.Accumulate.Mutations.Faster..........................158
12.6. Lessons.from.Small.Mammals:.Less.DHA,.Longer.Life.
Span........................................................................................159
12.7. Membrane.Pacemaker.Model.Is.Consistent.with.the.
Bowhead.Whale.as.Longest.Lived.Mammal.........................161
References.........................................................................................166
Chapter 13 Membranes.and.Cancer.....................................................................169
13.1. Retinoblastoma.Occurs.in.a.Tissue.with.the.Highest.
Levels.of.DHA.in.the.Body....................................................169
13.2. Heavy.Trafficking.of.DHA.within.the.Developing.Brain.
Might.Potentiate.Brain.Tumors.in.Children...........................171
13.3. DHA.Is.a.Major.Building.Block.for.Sperm.Membranes:.
Is.There.an.Increased.Risk.of.Cancer.in.the.Testes?..............172
13.4. Correlation.between.High.Levels.of.DHA.in.Blood.and.
Aggressive.Prostate.Cancer....................................................173
13.5. Chemotherapy.Patients.Are.Advised.Not.to.Take.Fish.
Oil.Supplements.....................................................................174
13.6. Asymmetrical.Phospholipids.as.Possible.Promoters.of.
Breast.Cancer.........................................................................174
13.7. Does.Generalized.Cellular.Energy.Deficiency.Govern.
Rates.of.Cancer-.Causing.Nuclear.Mutations?........................178
References.........................................................................................180
Section V DHA Links Aging and neurodegeneration
Chapter 14 Parkinson’s.Disease...........................................................................185
14.1. Parkinsonian.Chemicals.Likely.Act.by.Accelerating.
Energy-.Oxidative.Stresses.via.a.Chain.Reaction.Mechanism....185
14.2. MPTP:.A.Potent.Neurotoxin..................................................187
14.3. A.Closer.Look.at.MPTP.as.a.Mitochondrial.Energy.
Poison.versus.an.Oxidative.Threat.........................................188
14.4. Parkinsonian.Neurons.Are.Likely.Predisposed.to.Energy.
Stress.Making.Them.Extremely.Sensitive.to.Chemicals.
in.the.Environment.................................................................191
14.5. Neurotoxic.Damage.to.Parkinsonian.Neurons.May.
Recruit.Hyperactive.Microglia.Causing.More.Damage.........192
x Contents
14.6. Mitochondrial.Mutations.as.a.Genetic.Pacemaker.for.
Age-.Dependent.Parkinson’s...................................................192
14.7. Dual.Energy-.Pacemaker.Model.of.Age-.Dependent.
Parkinson’s.Disease................................................................193
References.........................................................................................195
Chapter 15 Prion.Diseases...................................................................................197
15.1. A.Spongy-.Brain.Disease.in.the.Highlands.of.New.Guinea....197
15.2. Prion.Replication.Is.an.Amazing.Process.and.Depends.
on.Dysfunctional.Protein.Processing.....................................199
15.3. Does.Energy.Play.a.Role.in.How.Prions.Pick.Their.First.
Neuron.Target?.......................................................................202
15.4. Prion-.Infected.Neurons.Might.Be.Subjected.to.
Membrane.Energy.Uncoupling.Caused.by.the.Prion.............204
15.5. Numerous.Pinpoint.Brain.Lesions.Caused.by.Prions.May.
Spread.as.the.Result.of.Microglial-.Mediated.Neuron.
Damage...................................................................................205
15.6. A.Protective.Gene.against.Kuru.Found.in.Survivors.of.
New.Guinea.Epidemic............................................................205
References.........................................................................................206
Chapter 16 Brain.Trauma–Induced.Dementia.....................................................209
16.1. High.Rates.of.Brain.Trauma.in.Sports.and.Combat..............209
16.2. Axon.Stretch.Model.of.Trauma-.Triggered.Alzheimer’s.........211
16.3. Inflammation.Model...............................................................214
16.4. Suicide.Peptide.Model............................................................217
16.5. Energy.Stress.Caused.by.DHA.Might.Link.the.Three.
Models....................................................................................218
References.........................................................................................219
Chapter 17 Alzheimer’s.Disease..........................................................................221
17.1. An.Individual.Energy-.Stressed.or.Damaged.Neuron.
Might.Generate.a.Focal.Point.for.Alzheimer’s.......................221
17.2. Spreading.from.a.Focal.Point.Might.Be.Caused.by.an.
Inflammatory.Cascade.Linking.DHA.and.Alzheimer’s.
Disease....................................................................................224
17.3. Blocking.Neuron.Death.in.a.Mouse.Model.of.Alzheimer’s.
Disease.by.Knockout.of.a.Key.Signaling.Receptor.on.
Microglia................................................................................226
17.4. Is.the.Toxic.Peptide.Tau.the.Long-.Awaited.Infective.
Agent.Causing.the.Spread.of.Alzheimer’s.Disease?..............227
17.5. DHA.Oxidation.Products.in.Cerebrospinal.Fluid.Help.
Validate.the.DHA.Principle...................................................227