Beneficial Effects of Fish Oil on Human Brain (eBook)

Preface 6
Acknowledgments 8
Contents 9
Abbreviations 16
About the Author 17
Fish Oil and Importance of Its Ingredients in Human Diet 18
1.1 Introduction 18
1.2 n-3 Fatty Acids in Fish Oil Capsules and Krill Oil Capliques 20
1.2.1 Availability of Purified Fish Oil and Krill Oil Preparations 21
1.2.2 Other n-3-Enriched Manufactured Products 25
1.3 Effects of Fish Oil on Human Health 25
1.4 Effects of Fish Oil on Heart 26
1.4.1 Antiinflammatory and Antiatherosclerotic Effects of Fish Oil 27
1.4.2 Antiarrythmic Effects of Fish Oil 28
1.4.3 Antithrombotic Effects of Fish Oil 30
1.4.4 Effect of n-3 Fatty Acids on Revascularization 31
1.4.5 n-3 or omega -3 Index and Heart Disease 32
1.5 Effects of Fish Oil on Brain 33
1.5.1 Effect of Fish Oil on Neural Membranes 33
1.5.2 Effect of Fish Oil on Neuritogenesis 34
1.5.3 Effect of n-3 Fatty Acids on Ion Channels 34
1.5.4 Effect of n-3 Fatty Acids on Receptors 35
1.6 Effects of Fish Oil on Lungs 35
1.7 Effects of Fish Oil on Kidneys 36
1.8 Effects of Fish Oil on Plasma Lipids 37
1.9 Effect of Fish Oil on Liver 39
1.10 n-3 Fatty Acids and Bleeding Tendency 41
1.11 Effect of n-3 Fatty Acids on Blood Pressure 41
1.12 Recommendations for Intake of n-3 Fatty Acids 42
1.13 Beneficial Effects of Olive Oil on Human Health 42
1.13.1 Effects of Olive Oil on Heart 42
1.13.2 Effects of Olive Oil on Brain 46
1.14 Harmful Effects of Trans Fatty Acids on Human Health 48
1.15 Conclusion 51
References 52
Transport, Synthesis, and Incorporation of n-3 and n-6 Fatty Acids in Brain Glycerophospholipids 63
2.1 Introduction 63
2.2 Transport of Dietary ARA and DHA to Brain 64
2.3 Importance of DHA in Neural Membranes 67
2.4 ARA and Its Importance in Neural Membranes 69
2.5 Biosynthesis of n-3 and n-6 Fatty Acids in Liver 70
2.5.1 Biosynthesis of n-3 Fatty Acids in Liver 71
2.5.2 Biosynthesis of n-6 Fatty Acids in Liver 74
2.6 Incorporation of Fatty Acids in Glycerophospholipids 76
2.6.1 Acyl-CoA Synthetases in Brain 77
2.6.2 Acyl-CoA:lysophospholipid Acyltransferase in Brain 80
2.6.3 CoA-Independent Reacylation in Brain 83
2.7 Incorporation of ALA and LA in Brain Lipids 83
2.8 Incorporation of Docosahexaenoic Acid in Neural Membranes in Glycerophospholipids 84
2.9 Incorporation of Arachidonic Acid in Neural Membranes 86
2.10 Conclusion 86
References 87
Release of n-3 and n-6 Fatty Acids from Glycerophospholipids in Brain 95
3.1 Introduction 95
3.2 Release of DHA from Ethanolamine or Choline Plasmalogen 96
3.2.1 Plasmalogen-Selective-Phospholipase A2 in Brain 97
3.2.2 Canine Myocardium PlsCho-PLA2 104
3.2.3 PlsEtn-PLA2 from Rabbit Kidney 105
3.3 Release of DHA from PtdSer 107
3.4 Receptor-Mediated Degradation of Plasmalogens 107
3.5 Release of n-6 Fatty Acids from Neural Membrane Glycerophospholipids 108
3.5.1 cPLA2 in Brain 108
3.5.2 Other Phospholipases A2 112
3.6 Regulation of PLA2 Activity in Brain 112
3.6.1 Regulation of PlsEtn-PLA2 112
3.6.2 Regulation of cPLA2 113
3.7 Conclusion 114
References 115
Oxidation of Arachidonic and Docosahexaenoic Acids and Neurochemical Effects of Their Metabolites on Brain 121
4.1 Introduction 121
4.2 Arachidonic Acid and Its Enzymic Oxidation in Brain 124
4.2.1 Isoforms of Cyclooxygenases in Brain 124
4.2.2 Roles of Eicosanoids in Brain 126
4.2.3 Isoforms of Lipoxygenases in Brain 128
4.2.4 Roles of Lipoxins in Brain 129
4.2.5 Isoforms of Cytochrome P450 Epoxygenases in Brain 132
4.2.6 cis-Epoxyeicosatrienoic Acids 134
4.3 Non-enzymic Oxidation of Arachidonic Acid 135
4.3.1 4-Hydroxynonenal, Acrolein, and Malondialdehyde 135
4.3.2 Isoprostanes 140
4.3.3 Isoketals 142
4.3.4 Isofurans 144
4.4 Enzymic and Non-enzymic Oxidation of DHA 144
4.4.1 Enzymic Oxidation of DHA 145
4.4.2 17S D Series Resolvins 146
4.4.3 Docosatrienes 147
4.5 Non-enzymic Oxidation of Docosahexaenoic Acid 149
4.5.1 4-Hydroxyhexenal 149
4.5.2 Neuroprostanes 150
4.5.3 Neuroketals 151
4.5.4 Neurofurans 152
4.6 Enzymic Oxidation of EPA in Brain 152
4.7 Non-enzymic Oxidation of EPA 154
4.8 Conclusion 156
References 156
Roles of Docosahexaenoic and Eicosapentaenoic Acids in Brain 166
5.1 Introduction 166
5.2 Comparison of Biochemical Activities of DHA and EPA 167
5.3 Role of DHA in Brain Tissue 171
5.3.1 DHA-Mediated Modulation of Physiocochemical Properties of Membranes 171
5.3.2 DHA-Mediated Modulation of Neurotransmission 172
5.3.3 DHA-Mediated Modulation of Gene Expression 173
5.3.4 DHA-Mediated Modulation of Enzymic Activities 174
5.3.5 DHA-Mediated Modulation of Inflammation and Immunity 176
5.3.6 DHA-Mediated Modulation of Learning and Memory 178
5.3.7 DHA-Mediated Modulation of Apoptosis 179
5.3.8 DHA and Generation of Docosanoids 181
5.3.9 DHA-Mediated Generation of Neurite Outgrowth 181
5.3.10 DHA-Mediated Modulation of Visual Function 183
5.3.11 DHA-Mediated Modulation of Nociception (Pain) 183
5.3.12 DHA, Plasma Membrane Targeting, and Raft Formation 184
5.4 Roles of EPA in Brain 185
5.4.1 EPA-Mediated Modulation of Inflammation and Immunity 186
5.4.2 EPA-Mediated Modulation of Depression 187
5.4.3 EPA-Mediated Modulation of Gene Expression 188
5.4.4 EPA-Mediated Modulation of Enzymic Activities 189
5.4.5 EPA and Generation of Resolvin E1 189
5.4.6 EPA-Mediated Modulation of Lipid Rafts 191
5.4.7 Other Roles of EPA 191
5.5 Conclusion 192
References 192
Status of Docosahexaenoic Acid Levels in Aging and Consequences of Docosahexaenoic Acid Deficiency in Normal Brain 203
6.1 Introduction 203
6.2 DHA and ARA Entry and Metabolism in Developing Brain 205
6.3 Alterations in DHA Levels in Various Regions During Aging 207
6.4 DHA in Plasmalogens and Phosphatidylserine 208
6.4.1 DHA in Plasmalogens 210
6.4.2 DHA in Phosphatidylserine 211
6.5 Consequences of DHA Deficiency in Brain 213
6.5.1 Effects of DHA Deficiency on Behavioral Parameters 215
6.5.2 Effects of DHA Deficiency on Glucose Utilization 215
6.5.3 Effects of DHA Deficiency on Lipid Metabolism 216
6.5.4 Effects of DHA Deficiency on Receptor Function 217
6.5.5 Effects of DHA Deficiency on Protein Function and Enzyme Activities 219
6.5.6 Effects of DHA Deficiency on Growth Factors 220
6.5.7 Effects of DHA Deficiency on Ion Channels Permeability 221
6.5.8 Effects of DHA Deficiency on Blood Pressure 222
6.6 Conclusion 222
References 223
Status and Potential Therapeutic Importance of n-3 Fatty Acids in Neurodegenerative Disease 231
7.1 Introduction 231
7.2 Apoptotic Cell Death in Neurodegenerative Diseases 236
7.3 Factors Influencing the Onset of Neurodegenerative Diseases 237
7.3.1 Genetic and Environmental Factors 238
7.3.2 Lifestyle and Neurodegenerative Diseases 239
7.3.3 Diet and Neurodegenerative Diseases 242
7.4 Importance of n-3 Fatty Acid in Diet 245
7.4.1 Docosahexaenoic Acid in Alzheimer Disease 246
7.4.2 Docosahexaenoic Acid in Parkinson Disease 252
7.4.3 Docosahexaenoic Acid in Amyotropic Lateral Sclerosis 256
7.4.4 Docosahexaenoic Acid in Huntington Disease 258
7.5 Interactions Among Excitotoxicity, Oxidative Stress, and Neuroinflammation in Neurodegenerative Diseases 258
7.6 Conclusion 262
References 263
Status and Potential Therapeutic Importance of n-3 Fatty Acids in Acute Metabolic Trauma and Neurotraumatic Disorders 275
8.1 Introduction 275
8.2 Similarities and Differences Between Ischemic and Traumatic Neural Injuries 276
8.3 Glycerophospholipids and Fatty Acids Alterations in Ischemic Injury 280
8.4 Effect of n- 3 Fatty Acids on Ischemic Injury 284
8.5 Glycerophospholipids, Fatty Acid, BDNF, and cAMP in Spinal Cord Injury 286
8.6 Effect of n-3 Fatty Acids on Spinal Cord Injury 288
8.7 Glycerophospholipid and Fatty Acids Alterations in Traumatic Brain Injury 289
8.8 Effect of n- 3 Fatty Acids on Traumatic Brain Injury 289
8.9 Glycerophospholipid and Fatty Acid Alterations in Epilepsy 291
8.10 Effect of n- 3 Fatty Acids on Epilepsy 292
8.11 Glycerophospholipids and Fatty Acids in Kainic Acid-Induced Neural Cell Injury 293
8.12 Effect of n-3 Fatty Acids in Kainic Acid-Induced Neural Cell Injury 294
8.13 Interactions Among Excitotoxicity, Oxidative Stress, and Neuroinflammation Following Acute Neural Trauma 295
8.14 Conclusion 297
References 298
Status and Potential Therapeutic Importance of n-3 Fatty Acids in Neuropsychiatric Disorders 307
9.1 Introduction 307
9.2 Oxidative Stress and Neuroinflammation in Neuropsychiatric Diseases 310
9.3 Dysregulation of Neurotransmission in Neuropsychiatric Diseases 311
9.4 BDNF-Mediated Signaling in Neuropsychiatric Disorders 313
9.5 Abnormalities in Essential Fatty Acid Levels and Neuropsychiatric Disorders 317
9.5.1 Fatty Acids and Glycerophospholipids in Schizophrenia 318
9.5.2 Fatty Acids and Glycerophospholipids in Depression and Bipolar Disorders 321
9.5.3 Fatty Acids and Glycerophospholipids in Dyslexia 323
9.5.4 Fatty Acids and Glycerophospholipids in Autism 324
9.6 Status of n-3 and n-6 Fatty Acids in Neuropsychiatric Disorders 325
9.6.1 n-6 and n-3 Fatty Acids in Depression and Bipolar Disorder 325
9.6.2 n-6 and n-3 Fatty Acids in Aggressive Disorders and Cocaine Addiction 327
9.6.3 n-6 and n-3 Fatty Acids in Attention-Deficit/Hyperactivity Disorder 327
9.7 Effects of n-3 Fatty Acid Supplementation in Neuropsychiatric Disorders 329
9.7.1 Depression and Bipolar Disorder 329
9.7.2 Treatment with Neuropsychiatric Disorders with High-Doses EPA 330
9.7.3 Treatment of ADHD with High-Doses EPA 330
9.8 Mechanism of Action of n-3 Fatty Acids in Neuropsychiatric Disorders 331
9.9 Involvement of Genes in Neuropsychiatric Disorders 333
9.10 Conclusion 334
References 335
Status and Potential Therapeutic Importance of n-3 Fatty Acids in Other Neural and Non-neural Diseases 347
10.1 Introduction 347
10.2 Effect of Fish Oil on Peroxisomes 347
10.3 Peroxisomes and Peroxisomal Disorders 348
10.3.1 Zellweger Syndrome 349
10.3.2 Adrenoleukodystrophy 350
10.4 Treatment of Peroxisomal Disorders with DHA 352
10.4.1 DHA and Adrenomyeloneuropathy 353
10.4.2 DHA, Retinitis Pigmentosa, and Retinopathy 353
10.5 DHA and Prion Diseases 354
10.6 DHA and Multiple Sclerosis 356
10.7 DHA and Non-neural Diseases 357
10.7.1 DHA and Chronic Obstructive Pulmonary Disease 358
10.7.2 DHA and Crohn’s Disease 360
10.7.3 DHA and Systemic Lupus Erythematosus 361
10.7.4 DHA and Cystic Fibrosis 362
10.7.5 DHA and Arthritis 365
10.7.6 DHA and Osteoporosis 368
10.7.7 DHA and Psoriasis 369
10.7.8 DHA and Its Clinical Trials in Chronic Diseases 370
10.8 Conclusion 371
References 372
Perspective and Directions for Future Development on the Effects of Fish Oil Constituents on Brain 380
11.1 Introduction 380
11.2 Chronic Diseases and Dietary n-6/n-3 Ratio 381
11.3 Expression of Genes in Animals and Plants to Improve n-6 to n-3 Fatty Acids Ratio 384
11.4 Unsolved Problems of DHA and ARA Metabolism 386
11.4.1 Characterization of Enzymes Associated with DHA and ARA Metabolism 387
11.4.2 Development of Antisense Oligonucleotides and RNAi 387
11.4.3 Characterization of Receptors for Neuroprotectins and Resolvins 388
11.5 Nutrigenomics/Nutrigenetics/Transcriptomics Approaches to n-3 Fatty Acids 389
11.6 Conclusion 392
References 393
Index 398