Functional Genomics and Proteomics in the Clinical Neurosciences: Volume 158(Volume 158 Progress in Brain Research)

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.

Table of Contents:
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