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The Neurochemical Basis of Autism - From Molecules to Minicolumns
von: Gene J. Blatt
Springer-Verlag, 2010
ISBN: 9781441912725 , 300 Seiten
Format: PDF, OL
Kopierschutz: Wasserzeichen
Preis: 149,79 EUR
Preface
8
Contents
12
Contributors
14
Autism Spectrum Disorders: Clinical and Medical Perspectives
17
Introduction
17
Etiology
17
Clinical Presentation
18
Associated Medical Disorders
21
Seizure Disorders
22
Gastrointestinal Disorders
23
Sleep Disorders
23
Metabolic Disorders
24
Conclusion
25
References
25
The Male Prevalence in Autism Spectrum Disorders: Hypotheses on its Neurobiological Basis
28
Introduction
28
Neuroanatomical and Neurofunctional Features of Autism Spectrum Disorders in Relationship to Brain Sexual Dimorphisms
29
Theories Accounting for the Male Prevalence of ASD
30
Hemispheric Lateralization, Brain Sexual Dimorphisms and Foetal Testosterone
30
Foetal Testosterone and Autism
32
The Role of Oestrogens in Sexually Dimorphic Anatomy and Behaviour
34
Oestrogens, Reelin and Cerebellar Circuits
37
Concluding Remarks: Making Sense of the Complexity
38
References
38
Neuroanatomical-Behavioral Correlates in Autism: A Working Hypothesis
44
Introduction
44
Neuroanatomical Abnormalities in Autism
44
Limbic and Cerebellar Abnormalities and their Functional Relationship with Autistic Symptoms
46
Amygdala
47
Septal Nuclei
50
Anterior Cingulate Cortex
51
Hippocampus
51
Cerebellum
52
Developmental Hypothesis
53
Conclusions
55
References
55
The Morphology of Minicolumns
59
Minicolumns
59
Physiologically Defined Units
60
Pyramidal Cell Modules: Anatomically Defined Units Based on Apical Dendrite Clustering
61
The Basic Structure of the Pyramidal Cell Modules
61
Apical Dendritic Clusters in the Neocortices of Other Animals
67
The Spatial Arrangement and Connections of Apical Dendritic Clusters
69
Myelinated Axon Bundles
70
Unmyelinated Axon Bundles
71
A Conclusion
71
Minicolumns Based on Vertical Arrays of Neuronal Cell Bodies Seen in Nissl Stained Sections
73
Alterations in Nissl Stained Minicolumns
76
Alzheimer's Disease
76
Normal Aging
77
Autism
77
References
79
The Developmental Neuropathology of Autism
83
Introduction
83
Cellular Neuropathology
83
Abnormal Postnatal Brain Growth
88
Relationship Between Cellular Pathology and Abnormal Brain Growth
90
Concluding Remarks on Abnormal Grain Growth
92
References
92
Understanding Alterations During Human Brain Development with Molecular Imaging: Role in Determining Serotonin and GABA Mechanisms in Autism
97
Studies of Brain Development with PET
97
Serotonin Synthesis
97
GABA A Receptors
98
Alteration of Serotonin Synthesis Capacity in Autism
98
Alterations of GABA A Receptor Binding in Autism
99
Pharmacological Intervention in Autism to Restore Neurochemical Developmental Patterns
99
Mechanisms of Serotonin Effects on Brain Development
100
Mechanisms of GABA Effects on Brain Development
101
Combining Pharmacological and Behavioral Interventions
103
Conclusion
103
References
104
Glutamic Acid Decarboxylase (GAD) as a Biomarker of GABAergic Activity in Autism: Impact on Cerebellar Circuitry and Function
108
Glutamic Acid Decarboxylase Activity Is Involved in the Modulation of GABA Levels
108
GABA as a Developmental Factor
110
Regional Distribution of GAD in Cerebellar Interneurons
111
Cerebellar Circuitry, Function, and the Region of Interest: Crus II Region in the Posterior Lobe in the Lateral Hemisphere
111
GAD Abnormalities in the Cerebellum in Autism
113
GAD67 mRNA Levels in Purkinje Cells in the Crus II Region
113
GAD67 mRNA Levels in Cerebellar Basket and Stellate Cells in the Crus II Region
113
GAD67 mRNA Levels in Golgi Cells in the Crus II Region
114
GAD65 mRNA Levels in the Dentate Nucleus
114
Altered GAD in the Lateral Cerebellar Hemisphere May Impact the Normal Functioning of Cerebellar Circuitry in Autism
114
Additional Functional Considerations
117
Concluding Notes and Ongoing Studies
118
References
119
Epigenetic Dysregulation of 15q11-13 GABAA Receptor Genes in Autism
125
GABA A Receptor Function and Genome Organization
125
Role of GABA in Brain Function
125
Genomic Clustering of the GABA A Receptor Genes in the Human Genome
126
Phenotypic Consequences of Disruption of Gaba a Receptors
127
Chromosome 15q11-13 and Neurodevelopmental Disorders
127
Prader--Willi and Angelman Syndromes
129
Rett Syndrome
129
Chromosome 15q11-13 Duplication Syndrome
130
Genetic Evidence for 15q11-13 Involvement in Autism
131
Linkage and Association Studies in Autism
131
GABRB3 Protein Defects in Autism Post-mortem Brain
131
Phenotypic Consequences of GABRB3 Deficiency
132
Complex Regulation of 15q11-13 GABA A Receptors
132
Paternal Expression Bias of 15q11-13 GABA A Receptor Genes
132
Aberrant Monoallelic Expression of 15q11-13 GABA A Receptor Subunits in Autism
133
Homologous Pairing of 15q11-13 Chromosomes in Neurons
133
References
134
Cholinergic Component of Autism Spectrum Disorder
140
Introduction
140
Abnormal Brain Development in Autism
140
The Excitatory/Inhibitory Ratio Theory
142
Cholinergic System
142
Post-mortem Studies
144
Muscarinic Receptor Changes in Autism
144
Nicotinic Receptor Changes in Autism
144
Growth Factors Modulating the Cholinergic System
147
Interpretations
148
Cholinergic Therapies for Autism
149
Acetylcholinesterase Inhibitors (ChEI)
149
ChEI Treatment in Schizophrenia
150
ChEI Treatment in Down Syndrome (DS)
150
ChEI Treatment in Autism
151
Nicotinic Agonists
162
Conclusions
162
References
164
Oxytocin and Autism
173
Introduction
173
Neurobiology of Oxytocin: Preclinical Studies
173
Neurobiology of Oxytocin Action in Humans
174
Oxytocin and Autism: Preliminary Evidence and Neurobiological Mechanisms
177
References
180
The Role of the Noradrenergic System in Autism SpectrumDisorders
184
Noradrenergic System and Autism
184
Noradrenergic System, Stress, and Cognition
185
Noradrenergic System, Cognition, and Autism
186
Mechanism of the Effects of the Noradrenergic System on Cognition
187
Future Directions
189
References
190
Oxidative Stress in Autism and Its Implications for Dopamine-Stimulated Phospholipid Methylation
194
Redox and Methylation
195
Redox Regulation in the Brain
196
Dopamine-Stimulated Phospholipid Methylation
200
Oxidative Stress and Neuroinflammation in Autism
202
The Autism/Vaccination Controversy
204
Future Directions
205
References
205
Neuroligins and Neurexins: Synaptic Bridges Implicated in Autism
209
Introduction
209
Neuroligins and Neurexin-1 as Candidate Autism Genes
210
Neurexins: Discovery, Domain Structure, and Brain Distribution
211
Neuroligins: Discovery, Domain Structure, and Brain Distribution
212
Role of Alternative Splicing in Neurexin/Neuroligin Interaction
213
Involvement of Neurexin/Neuroligin in Synapse Formation or Validation
214
Autism Animal Model Based on Neuroligin 3 Mutation
216
Future Questions and Mouse Models
219
References
220
The Neurophysical Chemistry of Autism: Postulates from Intelligence Modeling
224
Introduction
224
Defining the State of Autism for Input Into the Intelligence Modeling Paradigm
226
The Method of Intelligence Modeling and Cognitive Dynamics
227
A Paradigm for a Unified Theoretical Neuroscience
227
IM is a Distinct Program of Computational Neurology
228
The Systems Modeling Tools Used in IM and CDT
229
Intelligence Modeling is a Method of Scientific Model Building
230
The IM Process
231
Intelligence Modeling of Ambiguous Figures
233
Cognitive Dynamics Describes How Brains Assemble and Then Operate on Internal Mental Models
236
Cybernetic Action and the Principle of Least Cybernetic Action
238
A Cognitive Dynamics Treatment of Dogginess and Bearishness -- Complex Knowledge Interactions Map to Complex or Interacting Surfaces
239
The Cognitive Dynamics of Autism
241
Does Migraine Provide Insight into ASD?
243
Mechanistic Considerations in Autism
244
References
249
Pharmacological Treatment of Autism
251
Introduction
251
Secretin: A Cautionary Tale
252
Antidepressants
252
Stimulants
255
Antipsychotics
257
Anticonvulsants
261
Alpha 2 Adrenergic Antagonists
262
Melatonin
263
Naltrexone
263
Acetylcholinesterase Inhibitors
265
NMDA Receptor Antagonists
265
Benzodiazepines
266
Conclusion
267
References
267
Appendix: Lay Abstracts/Summary
274
Chapter 1: Autism Spectrum Disorders: Clinical and Medical Perspectives
274
Chapter 2: The Male Prevalence in Autism Spectrum Disorders: Hypotheses on Its Neurobiological Basis
274
Chapter 3: Neuroanatomical-Behavioral Correlates in Autism: A Working Hypothesis
275
Chapter 4: The Morphology of Minicolumns
276
Chapter 5: The Developmental Neuropathology of Autism
277
Chapter 6: Understanding Alterations During Human Brain Development with Molecular Imaging: Role in Determining Serotonin and GABA Mechanisms in Autism
277
Chapter 7: Glutamic Acid Decarboxylase (GAD) as a Biomarker of GABAergic Activity in Autism: Impact on Cerebellar Circuitry and Function
277
Chapter 8: Epigenetic Dysregulation of 15q11-13 GABA A Receptor Genes in Autism
278
Chapter 9: Cholinergic Component of Autism Spectrum Disorder
279
Chapter 10: Oxytocin and Autism
279
Chapter 11: The Role of the Noradrenergic System in Autism Spectrum Disorders
280
Chapter 12: Oxidative Stress in Autism and Its Implications for Dopamine-Stimulated Phospholipid Methylation
280
Chapter 13: Neuroligins and Neurexins: Synaptic Bridges Implicated in Autism
281
Chapter 14: The Neurophysical Chemistry of Autism: Postulates from Intelligence Modeling
281
Chapter 15: Pharmacological Treatment of Autism
282
Subject Index
284
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