Functional Genomics and Proteomics in the Clinical Neurosciences: Volume 158

ISBN-13: 9780444518538 / Angielski / Twarda / 2006 / 317 str.

S. E. Hemby; S. Bahn

Opis

The purpose of this work is to familiarize neuroscientists with the available tools for proteome research and their relative abilities and limitations. To know the identities of the thousands of different proteins in a cell, and the modifications to these proteins, along with how the amounts of both of these change in different conditions would revolutionize biology and medicine. While important strides are being made towards achieving the goal of global mRNA analysis, mRNA is not the functional endpoint of gene expression and mRNA expression may not directly equate with protein expression. There are many potential applications for proteomics in neuroscience: determination of the neuro-proteome, comparative protein expression profiling, post-translational protein modification profiling and mapping protein-protein interactions, to name but a few. Functional Genomics and Proteomics in Clinical Neuroscience will comment on all of these applications, but with an emphasis on protein expression profiling. This book combines the basic methodology of genomics and proteomics with the current applications of such technologies in understanding psychiatric illnesses.

* Introduction of basic methodologies in genomics and proteomics and their integration in psychiatry
* Development of the text in sections related to methods, application and future directions of these rapidly advancing technologies
* Use of actual data to illustrate many principles of functional genomics and proteomics.
* Introduction to bioinformatics and database management techniques

Spis treści

List of Contributors

Foreword

Functional Genomics and Proteomics in the Clinical Neurosciences

Tissue preparation and banking

Introduction

Identifying subjects

Collection and harvesting tissue

Documenting

RNA integrity

Protein integrity

Conclusions

Functional genomic methodologies

Introduction

Input sources of RNA

Gene expression profiling: toward an informed choice

Level of sensitivity to detect the molecules of interest

Magnitude of expression-level changes in the brain

Minimum starting material for functional genomic analysis

Verification of expression-profiling analysis

Conventional methods of analyzing gene expression: Northern hybridization

qPCR

Serial analysis of gene expression (SAGE)

Massive parallel signature sequencing (MPSS)

Total analysis of gene expression (TOGA)

Sequencing by hybridization (SBH)

Microarray platforms

Analyzing massive datasets

Regional and single cell assessment

RNA amplification strategies: aRNA amplification

Additional considerations

Conclusions

Methods for proteomics in neuroscience

Introduction

Subcellular fractionation

Expression proteomics

Functional proteomics

Mass spectrometry

Protein arrays

Conclusion

Functional genomics and proteomics in the clinical neurosciences: data mining and bioinformatics

Introduction

Experimental methods

Data analysis

Statistical analysis and pattern classification

Microarray case study

Interpretation and validation

Reproducibility of microarray studies: concordance of current analysis methods

Introduction

The data analysis pipeline

Assessment of data quality

Performance comparison

Validation

Implications for data mining

Summary and conclusions

The genomics of mood disorders

Introduction

Genetics of mood disorders: the progress

Neurobiological and neuroanatomical substrates of severe mood disorders

The pathophysiology of severe mood disorders: insights from recent gene profiling studies

Clues from animal models

Concluding remarks

Transcriptome alterations in schizophrenia: disturbing the functional architecture of the dorsolateral prefrontal cortex

Dysfunction of the DLPFC in schizophrenia

Types of transcriptome alterations in the DLPFC in schizophrenia

Causes of transcriptome alterations in the DLPFC in schizophrenia

Consequences of transcriptome alterations in the DLPFC in schizophrenia

Conclusions

Strategies for improving sensitivity of gene expression profiling: regulation of apoptosis in the limbic lobe of schizophrenics and bipolars

Introduction

Conclusions

Assessment of genome and proteome profiles in cocaine abuse

Introduction

Neuroanatomy of cocaine addiction

Functional genomics

Proteomics

Conclusion

Neuronal gene expression profiling: uncovering the molecular biology of neurodegenerative disease

Introduction

Alzheimer's disease

Determination of RNA within senile plaques and neurofibrillary tangles in AD

Single cell gene array analysis of hippocampal senile plaques in AD

Single cell gene analysis of hippocampal NFTs in AD

Regional gene expression profiling in the hippocampus in AD

Regional gene expression profiling in frontal and temporal neocortex in AD

Regional gene expression profiling in other AD-related brain regions

Single cell analysis of cholinergic basal forebrain (CBF) neurons in AD

Single cell profiling of galanin hyperinnervated CBF neurons in AD

Summary of gene expression profiling in AD

Parkinson's disease

Regional gene profiling of the substantia nigra in PD

Gene expression profiling of Lewy body-containing SNpc neurons in PD

Summary of gene expression profiling in PD

Schizophrenia

Regional gene expression profiling in frontal cortex in schizophrenia

Single cell gene profiling in the entorhinal cortex in schizophrenia

Multiple sclerosis

Gene profiling in multiple sclerosis

Creutzfeld-Jakob disease

Gene profiling in the aged brain

Single cell profiling of aged CA1 and CA3 hippocampal neurons

Gene regulation during the course of normal aging within the frontal cortex

Conclusions

Abbreviations

Epileptogenesis-related genes revisited

Introduction

Methods

Results and discussion

Concluding remarks

Abbreviations

Functional genomics of sex hormone-dependent neuroendocrine systems: specific and generalized actions in the CNS

Neural and genomic mechanisms for female mating behaviors

From lordosis to sexual arousal to generalized CNS arousal

From generalized CNS arousal to specific forms of arousal

Molecular biology of histamine receptors in CNS

α1B-Noradrenergic receptor signaling

μ and δ opioid receptor signaling

Summary and outlook

Abbreviations

Implications for the practice of psychiatry

Introduction

Proteomics

mRNA expression arrays (expressomics)

Whole genome SNP association studies

Use of convergent evidence

Future directions

Human brain evolution

Anatomical evolution

Protein sequence evolution

Gene expression evolution

Theory of gene expression evolution

Adaptive human brain evolution

Conclusion

Subject Index

Erratum to Progress in Brain Research Vol. 158 Functional Genomics and Proteomics in the Clinical Neurosciences Scott E. Hemby and Sabine Bahn