Janigro Mammalian Brain Development

1. Auflage 2009
ISBN: 978-1-60761-287-2
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 227 Seiten

Reihe: Contemporary Neuroscience

Denis Noble Nearly a decade after completion of the first draft of the entire Human Genome sequence we are in a better position to assess the nature and the consequences of that heroic achievement, which can be seen as the culmination of the molecular biological revolution of the second half of the twentieth century. The achievement itself was celebrated at the highest levels (President and Prime Minister) on both sides of the Atlantic, and rightly so. DNA sequencing has become sufficiently c- mon now, even to the extent of being used in law courts, that it is easy to forget how technically difficult it was and how cleverly the sequencing teams solved those problems in the exciting race to finish by the turn of the century [1, 2]. The fanfares were misplaced, however, in an important respect. The metaphors used to describe the project and its biological significance gave the impression to the public at large, and to many scientists themselves, that this sequence would reveal the secrets of life. DNA had already been likened to a computer program [3]. The 'genetic program' for life was therefore to be found in those sequences: A kind of map that had simply to be unfolded during development. The even more colo- ful 'book of life' metaphor gave the promise that reading that book would lead to a veritable outpouring of new cures for diseases, hundreds of new drug targets, and a brave new world of medicine.

Autoren/Hrsg.

Janigro, Damir

Inhaltsverzeichnis

1;Foreword;6
1.1;References;9
2;Contents;10
3;Contributors;12
4;Sexual Differentiation of the Brain: Genetic, Hormonal and Trophic Factors;14
4.1;1 Brain Sex Depends on Hormones and Genes;15
4.2;2 Neurotrophic Factors Are Important or Sexual Dimorphism;18
4.3;3 Conclusion;22
4.4;References;23
5;Life at the Interface Between a Dynamic Environment and a Fixed Genome: Epigenetic Programming of Stress Responses by Maternal Behavior;29
5.1;1 Early in Life Environmental Influences on Brain Development and Behavioral Responses;30
5.2;2 Maternal Care in the Rat and HPA and Behavioral Responses to Stress in Adulthood;31
5.3;3 Molecular Mechanisms for Maternal Effects on HPA Responses to Stress;33
5.4;4 Maternal Care Epigenetically Programs HPA Stress Responses in the Offspring;35
5.5;5 Epigenetic Programming by Maternal Care is Reversible in the Adult Animal;37
5.6;6 Mechanisms Leading from Maternal Care to Chromatin Plasticity;38
5.7;7 Persistent Alterations in DNA Methylation and Phenotypic Plasticity;40
5.8;8 Modeling Variations in Maternal Care-Mediated Epigenetic Programming in Humans;43
5.9;9 Concluding Remarks;44
5.10;References;45
6;Effects of Early Life Seizures and Anti-epileptic Drug Treatment on Human Brain Development in Human Models;52
6.1;1 Introduction;52
6.2;2 Caveats to Clinical Research on Effects of Seizures and AEDs During Development;53
6.3;3 Developmental Impact of Early Life Seizures;54
6.4;4 Clinical Studies on Epilepsy and Cognition;55
6.5;5 Does Exposure to AEDs Affect the Developing Brain;57
6.5.1;5.1 Pregnancy Related Studies;58
6.5.2;5.2 Early Childhood Exposure;58
6.6;6 Conclusions/Future Directions;60
6.7;References;60
7;Prenatal Development of the Human Blood- Brain Barrier;64
7.1;1 Brain Development;65
7.1.1;1.1 The Brain Develops From the Inside-out;67
7.1.2;1.2 Maturation of Nerve Cells;68
7.2;2 Vascular Differentiation and BBB Development ;69
7.2.1;2.1 Origin of the Vascular Endothelial Cells;69
7.2.2;2.2 Induction and Formation of the Blood-Brain Barrier;70
7.2.3;2.3 Functional Characteristics of the BBB;73
7.2.4;2.4 Modulation of the Blood-Brain Barrier Tight Junction;75
7.3;3 Role of BBB in the Development of Neurological Disease;76
7.4;4 Pre-natal Pharmacological Treatment and Developmental Neurotoxicity;77
7.5;5 Brain Development and BBB: Extrapolating Animal Data to Human Studies;79
7.6;6 Conclusion;80
7.7;References;81
8;Seizure Propensity and Brain Development: A Lesson from Animal Models;87
8.1;1 Introduction;87
8.2;2 Are Immature Animals More Susceptible to Seizures? ;88
8.2.1;2.1 Chemoconvulsant Drugs;88
8.2.2;2.2 Electrically-Induced Seizures;92
8.2.3;2.3 Febrile Seizures;93
8.2.4;2.4 Cortical Malformations;94
8.2.5;2.5 Genetic Models;96
8.3;3 Long-Term Consequences ;99
8.3.1;3.1 Cell Damage and Network Plasticity;99
8.3.2;3.2 Spontaneous Seizures;100
8.4;4 Mechanisms Underlying Changes in Seizure Propensity;101
8.4.1;4.1 Ictogenesis;101
8.4.2;4.2 Epileptogenesis;102
8.5;5 Conclusions;103
8.6;References;103
9;Seizures and Antiepileptic Drugs: Does Exposure Alter Normal Brain Development in Animal Models?;115
9.1;1 Introduction;116
9.2;2 Effects of Seizures on Brain Development;116
9.3;3 Effects of Seizures;117
9.3.1;3.1 Triggered Seizures in Naive Brain;117
9.3.2;3.2 Seizures in the Abnormal Brain;122
9.3.3;3.3 Genetic Models;124
9.4;4 Effects of Administration of Antiepileptic Drugs ;125
9.4.1;4.1 Studies on Naïve Rats;125
9.4.2;4.2 Studies on Rats with Prior Experience of Seizures, Stress or Excitotoxic Insults;129
9.4.3;4.3 Candidate Mechanisms for the Effects of Antiepileptics on Brain Development;130
9.5;5 Additional Confounders;132
9.6;6 Conclusions;132
9.7;References;133
10;Overview of Neural Mechanisms in Developmental Disorders;143
10.1;1 Mechanisms of Development ;144
10.1.1;1.1 Neurulation;144
10.1.2;1.2 Neural Migration;146
10.1.3;1.3 Neural Network Pruning;147
10.2;2 Developmental Disorder Pathology ;148
10.2.1;2.1 Neural Tube Defects;148
10.2.2;2.2 Neural Migration Errors;150
10.2.3;2.3 Pervasive Developmental Disorders;152
10.2.4;2.4 Attention Deficit Hyperactivity Disorder;153
10.2.5;2.5 Anxiety Disorders;153
10.2.6;2.6 Prenatal Infectious Disease Exposure or Inflammation Mediated Response;154
10.2.7;2.7 Cerebral Palsy;157
10.3;3 Conclusion;158
10.4;References;159
11;Drug Permeation Across the Fetal Maternal Barrier;162
11.1;1 Introduction ;162
11.2;2 Anatomy and Development of the Placenta;162
11.3;3 Levels of Protection at the Placental Barrier;165
11.4;4 Metabolic Properties of the Placenta;166
11.5;5 Mechanisms of Drug Passage Across the Placenta;167
11.5.1;5.1 Drug Distribution: Similarities Between BBB and Blood-Placental Barrier;167
11.5.2;5.2 Drug Physical Properties Affecting Placental Permeability;168
11.5.3;5.3 Passive Diffusion;169
11.5.4;5.4 Facilitated Diffusion;169
11.5.5;5.5 Active Transport;169
11.5.6;5.6 Efflux Transporters;170
11.5.7;5.7 Influx/Efflux Transporters;173
11.6;6 Fate of Drugs in Pregnancy ;174
11.6.1;6.1 Does Serum Protein Play a Role in Drug Delivery During Pregnancy?;174
11.7;7 Xenobiotics Percolation Through the Placenta;174
11.8;8 Fetal-Maternal Unit Along with Developing Blood- Brain Barrier;175
11.9;References;176
12;In Vivo Imaging of Brain Development: Technologies, Models, Applications, and Impact on Understanding the Etiology of Mental Retardation;180
12.1;1 Introduction;180
12.2;2 Rational for In Vivo Imaging;181
12.3;3 In Vivo Imaging Technologies;182
12.3.1;3.1 Non-optical Imaging Techniques;183
12.3.2;3.2 Optical and Biophotonic Techniques;183
12.3.3;3.3 Advances in Labeling Methods;185
12.4;4 In Vivo Imaging Models;188
12.4.1;4.1 Dissociated Embryonic Brain Cell Cultures;188
12.4.2;4.2 Embryonic Brain Slices;188
12.4.3;4.3 Imaging in the Living Experimental Animals;189
12.5;5 The Impact of In Vivo Imaging on Studies of Cortical Development and Pathogenesis of Neurological Disorders;190
12.5.1;5.1 Neuronal Proliferation;190
12.5.2;5.2 Neuronal Migration;191
12.5.3;5.3 Development of Neuronal Connections;192
12.5.4;5.4 Advanced Microscopic Imaging in Animal Models of Neurological Diseases;193
12.5.5;5.5 Functional Imaging in Developmental Neurobiology;193
12.6;6 Future Directions;194
12.7;7 Conclusion;195
12.8;References;196
13;Congenital, Non-inheritable Chromosomal Abnormalities Responsible for Neurological Disorders;202
13.1;1 Introduction;202
13.2;2 Chromosomal Abnormalities and Cognitive Deficits;203
13.2.1;2.1 Mental Retardation;206
13.2.2;2.2 Brain Malformations;207
13.2.3;2.3 Neurological Dysfunctions;208
13.3;3 Animal Models of Chromosomal Abnormalities;209
13.4;4 Chromosomal Abnormalities and Synaptic Connections;209
13.4.1;4.1 Development of Brain Neuronal Networks;210
13.4.2;4.2 Molecular Mechanisms of Abnormal Brain Development;210
13.4.3;4.3 Synaptic Transmission and Plasticity;214
13.5;5 Conclusions;215
13.6;References;215
14;Index;228