Mammalian Brain Development (eBook)

Foreword 6
References 9
Contents 10
Contributors 12
Sexual Differentiation of the Brain: Genetic, Hormonal and Trophic Factors 14
1 Brain Sex Depends on Hormones and Genes 15
2 Neurotrophic Factors Are Important or Sexual Dimorphism 18
3 Conclusion 22
References 23
Life at the Interface Between a Dynamic Environment and a Fixed Genome: Epigenetic Programming of Stress Responses by Maternal Behavior 29
1 Early in Life Environmental Influences on Brain Development and Behavioral Responses 30
2 Maternal Care in the Rat and HPA and Behavioral Responses to Stress in Adulthood 31
3 Molecular Mechanisms for Maternal Effects on HPA Responses to Stress 33
4 Maternal Care Epigenetically Programs HPA Stress Responses in the Offspring 35
5 Epigenetic Programming by Maternal Care is Reversible in the Adult Animal 37
6 Mechanisms Leading from Maternal Care to Chromatin Plasticity 38
7 Persistent Alterations in DNA Methylation and Phenotypic Plasticity 40
8 Modeling Variations in Maternal Care-Mediated Epigenetic Programming in Humans 43
9 Concluding Remarks 44
References 45
Effects of Early Life Seizures and Anti-epileptic Drug Treatment on Human Brain Development in Human Models 52
1 Introduction 52
2 Caveats to Clinical Research on Effects of Seizures and AEDs During Development 53
3 Developmental Impact of Early Life Seizures 54
4 Clinical Studies on Epilepsy and Cognition 55
5 Does Exposure to AEDs Affect the Developing Brain 57
5.1 Pregnancy Related Studies 58
5.2 Early Childhood Exposure 58
6 Conclusions/Future Directions 60
References 60
Prenatal Development of the Human Blood- Brain Barrier 64
1 Brain Development 65
1.1 The Brain Develops From the Inside-out 67
1.2 Maturation of Nerve Cells 68
2 Vascular Differentiation and BBB Development 69
2.1 Origin of the Vascular Endothelial Cells 69
2.2 Induction and Formation of the Blood-Brain Barrier 70
2.3 Functional Characteristics of the BBB 73
2.4 Modulation of the Blood-Brain Barrier Tight Junction 75
3 Role of BBB in the Development of Neurological Disease 76
4 Pre-natal Pharmacological Treatment and Developmental Neurotoxicity 77
5 Brain Development and BBB: Extrapolating Animal Data to Human Studies 79
6 Conclusion 80
References 81
Seizure Propensity and Brain Development: A Lesson from Animal Models 87
1 Introduction 87
2 Are Immature Animals More Susceptible to Seizures? 88
2.1 Chemoconvulsant Drugs 88
2.2 Electrically-Induced Seizures 92
2.3 Febrile Seizures 93
2.4 Cortical Malformations 94
2.5 Genetic Models 96
3 Long-Term Consequences 99
3.1 Cell Damage and Network Plasticity 99
3.2 Spontaneous Seizures 100
4 Mechanisms Underlying Changes in Seizure Propensity 101
4.1 Ictogenesis 101
4.2 Epileptogenesis 102
5 Conclusions 103
References 103
Seizures and Antiepileptic Drugs: Does Exposure Alter Normal Brain Development in Animal Models? 115
1 Introduction 116
2 Effects of Seizures on Brain Development 116
3 Effects of Seizures 117
3.1 Triggered Seizures in Naive Brain 117
3.2 Seizures in the Abnormal Brain 122
3.3 Genetic Models 124
4 Effects of Administration of Antiepileptic Drugs 125
4.1 Studies on Naïve Rats 125
4.2 Studies on Rats with Prior Experience of Seizures, Stress or Excitotoxic Insults 129
4.3 Candidate Mechanisms for the Effects of Antiepileptics on Brain Development 130
5 Additional Confounders 132
6 Conclusions 132
References 133
Overview of Neural Mechanisms in Developmental Disorders 143
1 Mechanisms of Development 144
1.1 Neurulation 144
1.2 Neural Migration 146
1.3 Neural Network Pruning 147
2 Developmental Disorder Pathology 148
2.1 Neural Tube Defects 148
2.2 Neural Migration Errors 150
2.3 Pervasive Developmental Disorders 152
2.4 Attention Deficit Hyperactivity Disorder 153
2.5 Anxiety Disorders 153
2.6 Prenatal Infectious Disease Exposure or Inflammation Mediated Response 154
2.7 Cerebral Palsy 157
3 Conclusion 158
References 159
Drug Permeation Across the Fetal Maternal Barrier 162
1 Introduction 162
2 Anatomy and Development of the Placenta 162
3 Levels of Protection at the Placental Barrier 165
4 Metabolic Properties of the Placenta 166
5 Mechanisms of Drug Passage Across the Placenta 167
5.1 Drug Distribution: Similarities Between BBB and Blood-Placental Barrier 167
5.2 Drug Physical Properties Affecting Placental Permeability 168
5.3 Passive Diffusion 169
5.4 Facilitated Diffusion 169
5.5 Active Transport 169
5.6 Efflux Transporters 170
5.7 Influx/Efflux Transporters 173
6 Fate of Drugs in Pregnancy 174
6.1 Does Serum Protein Play a Role in Drug Delivery During Pregnancy? 174
7 Xenobiotics Percolation Through the Placenta 174
8 Fetal-Maternal Unit Along with Developing Blood- Brain Barrier 175
References 176
In Vivo Imaging of Brain Development: Technologies, Models, Applications, and Impact on Understanding the Etiology of Mental Retardation 180
1 Introduction 180
2 Rational for In Vivo Imaging 181
3 In Vivo Imaging Technologies 182
3.1 Non-optical Imaging Techniques 183
3.2 Optical and Biophotonic Techniques 183
3.3 Advances in Labeling Methods 185
4 In Vivo Imaging Models 188
4.1 Dissociated Embryonic Brain Cell Cultures 188
4.2 Embryonic Brain Slices 188
4.3 Imaging in the Living Experimental Animals 189
5 The Impact of In Vivo Imaging on Studies of Cortical Development and Pathogenesis of Neurological Disorders 190
5.1 Neuronal Proliferation 190
5.2 Neuronal Migration 191
5.3 Development of Neuronal Connections 192
5.4 Advanced Microscopic Imaging in Animal Models of Neurological Diseases 193
5.5 Functional Imaging in Developmental Neurobiology 193
6 Future Directions 194
7 Conclusion 195
References 196
Congenital, Non-inheritable Chromosomal Abnormalities Responsible for Neurological Disorders 202
1 Introduction 202
2 Chromosomal Abnormalities and Cognitive Deficits 203
2.1 Mental Retardation 206
2.2 Brain Malformations 207
2.3 Neurological Dysfunctions 208
3 Animal Models of Chromosomal Abnormalities 209
4 Chromosomal Abnormalities and Synaptic Connections 209
4.1 Development of Brain Neuronal Networks 210
4.2 Molecular Mechanisms of Abnormal Brain Development 210
4.3 Synaptic Transmission and Plasticity 214
5 Conclusions 215
References 215
Index 228