Hot Topics in Neural Membrane Lipidology

Preface

Acknowledgments

Contents

List of Abbreviations

About the Author

1 Neural Membranes: A Pandora’s Box of Lipid Mediators

1.1 Lipid Composition of Neural Membranes

1.2 Glycerophospholipids and Their Metabolism in Brain

1.3 Arachidonic Acid and Its Enzymically Derived Oxidation Products

1.3.1 Arachidonic Acid and Lyso-glycerophospholipids

1.3.2 Lysophosphatidylcholine (lyso-PtdCho)

1.3.3 Eicosanoids

1.3.4 Lipoxins

1.4 Non-enzymic Oxidation of Arachidonic Acid

1.4.1 4-Hydroxynonenal (4-HNE)

1.4.2 Isoprostanes

1.4.3 Isoketals

1.4.4 Isofurans

1.5 Enzymic and Non-enzymic Oxidation of DHA

1.5.1 Enzymically Derived Lipid Mediators of DHA

1.5.2 Resolvins

1.5.3 Protectins and Neuroprotectins

1.6 Non-enzymic Oxidation of Docosahexaenoic Acid

1.6.1 4-Hydroxyhexenal

1.6.2 Neuroprostanes

1.6.3 Neuroketals (NK)

1.7 Sphingolipid Metabolism in Brain

1.7.1 Ceramide and Ceramide 1-Phosphate

1.7.2 Sphingosine and Sphingosine 1-Phosphate

1.8 Cholesterol Metabolism in Brain

1.9 Association of Lipid Mediators with Neurological Disorders

1.10 Conclusion

References

2 Interplay Among Glycerophospholipid, Sphingolipid, and Cholesterol-Derived Lipid Mediators in Brain: A Matter of Life and Death

2.1 Introduction

2.2 Generation of Glycerophospholipid-Derived Lipid Mediators

2.3 Enzymically-Derived AA Metabolites and Neuroinflammation

2.4 Platelet-Activating Factor in Brain

2.5 Metabolism of Sphingolipid-Derived Lipid Mediators in Brain

2.6 Neurochemical Effects and Roles of Ceramides

2.7 Generation of Cholesterol-Derived Metabolites in Brain

2.8 Interactions Among Phospholipid, Sphingolipid, and Cholesterol-Derived Lipid Mediators

2.8.1 Interactions Between Glycerophospholipid and Sphingolipid Metabolism

2.8.2 Interactions Between Glycerophospholipid and Sphingolipid-Derived Lipid Mediators

2.8.3 Interactions Between Glycerophospholipid and Cholesterol-Derived Lipid Mediators

2.8.4 Interactions Between Sphingolipid and Cholesterol-Derived Lipid Mediators

2.9 Conclusion

References

3 Janus Face of Phospholipase A2: Role of Phospholipase A2 in Neural Cell Survival and Death

3.1 Introduction

3.2 Multiplicity of PLA2 in Brain Tissue

3.2.1 Cytosolic Phospholipase A2 (cPLA2)

3.2.2 Calcium Independent Phospholipase A2(iPLA2)

3.2.3 Secretory Phospholipase A2 (sPLA2)

3.2.4 Plasmalogen Selective Phospholipase A2 (PlsEtn-PLA2)

3.3 Role of Multiple Forms of PLA2 in Brain

3.3.1 Multiple Forms of PLA2 and Neurotransmitter Release

3.3.2 Multiple Forms of PLA2 in Long-Term Potentiation and Long-Term Depression

3.3.3 Multiple Forms of PLA2 in Membrane Repair

3.3.4 Multiple Forms of PLA2 in Modulation of Neurite Outgrowth and Regeneration

3.3.5 Multiple Forms of PLA2 in Tubule Formation and Membrane Trafficking

3.3.6 Multiple Forms of PLA2 in the Cell Cycle

3.3.7 Multiple Forms of PLA2 in Neuroinflammation

3.3.8 Multiple Forms of PLA2 in Nociception and Vacuous Chewing Movements

3.3.9 Multiple Forms of PLA2 in Oxidative Stress

3.3.10 Multiple Forms of PLA2 in Apoptotic and Necrotic Cell Death

3.3.11 Multiple Forms of PLA2 in Chemotaxis

3.4 Regulation of Multiple Forms of PLA2 Activity in Brain

3.4.1 Regulation of cPLA2

3.4.2 Regulation of iPLA2

3.4.3 Regulation of sPLA2

3.5 Conclusion

References

4 Glycerophospholipid Metabolism in the Nucleus: Cross Talk Among Phospholipase A2, Phospholipase C and Phospholipase D

4.1 Introduction

4.2 Phospholipid Metabolism in the Nucleus

4.3 Importance of Phospholipases and Glycerophospholipid Metabolism in the Nucleus

4.4 Occurrence of Isoforms of Phospholipase A2, Phospholipase C, and Phospholipase D in Nucleus

4.4.1 PLA2 Activities in the Nucleus

4.4.2 Nuclear PLC Activities

4.4.3 Nuclear PLD Activities

4.5 Interplay Among Nuclear and Non-Nuclear PLA2, PLC, and PLD Activities

4.6 Nuclear PLA2, PLC, and PLD and Nuclear Inclusions in Neurological Disorders

4.7 Conclusion

References

5 Ether Glycerophospholipids: The Workhorse Lipids of Neural Membranes

5.1 Introduction

5.2 Plasmalogens in Brain

5.3 Biosynthesis of Plasmalogens

5.4 Degradation of Plasmalogens

5.4.1 Plasmalogen-Selective Phospholipase A2 (PlsEtn-PLA2)

5.4.2 Receptor-Mediated Degradation of Plasmalogens

5.5 Roles of Plasmalogens in Brain

5.6 Platelet-Activating Factor (PAF)

5.7 Biosynthesis of PAF

5.7.1 Remodeling Pathway

5.7.2 De Novo Synthesis of PAF

5.7.3 Oxidative Fragmentation Pathway for PAF Synthesis

5.8 Catabolism of PAF

5.8.1 Mammalian Brain Type I PAF-Acetyl Hydrolases

5.8.2 Type II PAF-Acetyl Hydrolases in Mammalian Tissues

5.8.3 PAF-Acetyl Hydrolases in Mammalian Plasma

5.9 Roles of PAF in Brain

5.10 Involvement of Plasmalogens in Neurological Disorders

5.10.1 Plasmalogens in Ischemic Injury

5.10.2 Plasmalogens in Alzheimer Disease

5.10.3 Plasmalogens in Spinal Cord Injury

5.10.4 Plasmalogens in Peroxisomal Disorders

5.11 Involvement of Platelet-Activating Factor in Neurological Disorders

5.12 Conclusion

References

6 Excitotoxicity-Mediated Neurochemical Changes in Neurological Disorders

6.1 Introduction

6.2 Glutamate-Mediated Neurochemical Changes in Brain

6.2.1 Glutamate-Mediated Changes in Arachidonic Acid and Lysophosphatidylcholine Metabolism

6.2.2 Glutamate-Mediated Changes in Platelet-Activating Factor Metabolism

6.2.3 Glutamate-Mediated Alterations in Eicosanoid Metabolism

6.2.4 Glutamate-Mediated Generation of Reactive Oxygen Species

6.2.5 Glutamate-Mediated Depletion of Reduced Glutathione

6.2.6 Glutamate-Mediated Alterations in Nuclear Transcription Factor kappaB (NF-kappaB)

6.2.7 Glutamate-Mediated Changes in Enzymic Activities

6.2.8 Glutamate-Mediated Expression of Cytokines

6.2.9 Glutamate-Mediated Changes in Growth Factors

6.2.10 Glutamate-Mediated Changes in Heat Shock Protein Expression

6.2.11 Glutamate-Mediated Upregulation of Genes

6.2.12 Glutamate and Apoptotic Neural Cell Death

6.3 Mechanism of Glutamate-Mediated Neural Cell Injury in Neurological Disorders

6.4 Involvement of Excitotoxicity in Neurological Disorders

6.4.1 Glutamate in Ischemic Injury

6.4.2 Glutamate in Spinal Cord Injury

6.4.3 Glutamate in Head Injury

6.4.4 Glutamate in Epilepsy

6.4.5 Glutamate in Alzheimer Disease

6.4.6 Glutamate in Amyotrophic Lateral Sclerosis (ALS)

6.4.7 Glutamate in Huntington Disease

6.4.8 Glutamate in AIDS Dementia Complex

6.4.9 Glutamate in Creutzfeldt-Jakob Disease (CJD)

6.4.10 Glutamate in Multiple Sclerosis (MS)

6.4.11 Domoic Acid Neurotoxicity

6.5 Conclusion

References

7 Recent Developments on Kainate-Mediated Neurotoxicity and Their Association with Generation of Lipid Mediators

7.1 Introduction

7.2 KA Receptor-Mediated Ion Fluxes in Neural Cells

7.3 KA-Mediated Alterations in Neural Membrane Glycerophospholipids

7.4 KA-Mediated Alterations in Sphingolipid Metabolism

7.5 Cholesterol Metabolism in Brain

7.5.1 KA-Mediated Changes in Cholesterol and Its Metabolites

7.5.2 KA-Mediated Alterations in Oxycholesterols

7.5.3 KA-Mediated Changes in Steroid Hormones

7.6 Consequences of Interactions Among Glycerophospholipid, Sphingolipid, and Cholesterol-Derived Lipid Mediators in KA-Mediated Neurotoxicity

7.7 Interactions Between Ceramide and Cholesterol Metabolism in KA-Mediated Toxicity

7.8 Interactions Between Glycerophospholipid and Cholesterol Metabolism in KA-Mediated Neurotoxicity

7.9 Conclusion

References

8 Beneficial Effects of Docosahexaenoic Acid on Health of the Human Brain

8.1 Introduction

8.2 Synthesis of DHA in Brain

8.3 Transport and Incorporation of Docosahexaenoic Acid in Brain

8.4 Release and Catabolism of DHA in Brain

8.5 Role of DHA in Brain Tissue

8.5.1 Modulation of Gene Expression by DHA

8.5.2 Modulation of Enzymic Activities by DHA

8.5.3 Modulation of Inflammation and Immunity by DHA

8.5.4 Modulation of Learning and Memory by DHA

8.5.5 Modulation of Apoptotic Cell Death by DHA

8.5.6 DHA and Generation of Docosanoids

8.5.7 DHA and Neurite Outgrowth

8.5.8 DHA in Visual Function

8.5.9 DHA in Nociception (Pain)

8.6 Alterations in DHA Levels in Aging and Neurological Disorders

8.6.1 DHA Levels in Normal Aging Brain

8.6.2 DHA Levels in Neurological Disorders

8.6.3 Dietary DHA and Cancer

8.7 The Adverse Effects of DHA

8.8 Conclusion

References

9 Effects of Statins and n-3 Fatty Acids on Heart and Brain Tissues: The Clash of the Titans

9.1 Introduction

9.2 Properties, Metabolic Sites and Mechanism of Action of Statins

9.3 Composition of Fish Oil and Its Importance in Human Nutrition

9.4 Biochemical Effects of Statins on Cardiovascular System

9.5 Biochemical Effects of Statins on Brain

9.5.1 Cholesterol-Independent Effects of Statins

9.5.2 Cholesterol-Dependent Effects of Statins

9.6 Biochemical Effects of Fish Oil on Heart

9.7 Biochemical Effects of Fish Oil on Brain

9.8 Therapeutic Value of Statins and DHA in Cardiovascular and Cerebrovascular Systems Disorders

9.8.1 Statins in Cardiovascular System

9.8.2 Stains in Cerebrovascular System

9.8.3 n-3 Fatty Acids in Cardiovascular System

9.8.4 n-3 Fatty Acids in Cerebrovascular System

9.9 Effects of Combination of Statin and Fish Oil in Cardiovascular and Neurological Disorders

9.10 Adverse Effects of Statins and n-3 Fatty Acids

9.11 Conclusions

References

10 Apoptosis and Necrosis in Brain: Contribution of Glycerophospholipid, Sphingolipid, and Cholesterol-Derived Lipid Mediators

10.1 Introduction

10.2 Apoptosis and Necrosis Death in Brain

10.2.1 Mechanisms Associated with the Activation of Caspases

10.2.2 Biochemical Changes Associated with Apoptosis

10.2.3 Biochemical Changes Associated with Necrosis

10.3 Apoptosis and Necrosis-Mediated Alterations in Glycerophospholipid, Sphingolipid, and Cholesterol Metabolism

10.3.1 Apoptosis and Necrosis-Mediated Changes in Glycerophospholipid Metabolism

10.3.2 Apoptosis and Necrosis-Mediated Changes in Sphingolipid Metabolism

10.3.3 Apoptosis and Necrosis-Mediated Changes in Cholesterol Metabolism

10.4 Interactions Among Glycerophospholipid, Sphingolipid, and Cholesterol Metabolism in Apoptosis and Necrosis

10.5 Apoptotic and Necrotic Cell Death in Neurological Disorders

10.6 Association of Mitochondrial Dysfunction with Apoptotic and Necrotic Cell Death in Neurological Disorders

10.7 Prevention of Apoptotic Cell Death by Inhibitors of Enzymes Associated with Exicitoxicity, Inflammation, and Oxidative Stress

10.7.1 Glutamate Receptor Antagonists

10.7.2 Antioxidants and Anti-inflammatory Agents

10.7.3 Prevention of Apoptosis by Inhibitors of Caspases, Calpains, PLA2, Nitric Oxide Synthase, and SMase

10.8 Conclusion

References

11 Perspective and Directions for Future Developments on Glycerophospholipid-, Sphingolipid-, and Cholesterol-Derived Lipid Mediators

11.1 Introduction

11.2 Association of Lipid Mediators with Neural Cell Death

11.3 Detection and Levels of Lipid Mediators in Neurological Disorders by Lipidomics

11.4 Detection of Lipid Mediators by Positron Emission Tomography

11.5 Proteomics, Enzymes of Lipid Metabolism, and Neurodegenerative Diseases

11.6 Antisense and RNAi as Neuroprotective Agents

11.7 Significance of Developing Early Detection Procedures and Treatment for Neurodegenerative Diseases

11.8 Conclusion

References

Index