Wavelet analysis of gene expression (WAGE)

The wavelet transform (WT) is the mathematical operator of choice for the analysis of nonstationary signals. At the same time, it is also a modelling operator that may be used to impose functional constraints on data to unveil hidden groupings and relationships. In this work, we apply the WT to the chromosomal sequences of gene expression values measured with microarray technology. The application of the wavelet operator aims to uncover clusters of genes that interact by vicinity, either because of a shared regulatory mechanism or because of common susceptibility to environmental factors. Application of the method to data on the expression of human brain genes in neuro-degeneration validates the technique and, at the same time, illustrates the potential of the method

Wavelet analysis of gene expression (WAGE)

The wavelet transform (WT) is the mathematical operator of choice for the analysis of nonstationary signals. At the same time, it is also a modelling operator that may be used to impose functional constraints on data to unveil hidden groupings and relationships. In this work, we apply the WT to the chromosomal sequences of gene expression values measured with microarray technology. The application of the wavelet operator aims to uncover clusters of genes that interact by vicinity, either because of a shared regulatory mechanism or because of common susceptibility to environmental factors. Application of the method to data on the expression of human brain genes in neuro-degeneration validates the technique and, at the same time, illustrates the potential of the method

Translating the cellular neuropathology of microglia into neuroimaging results

The brain responds to the challenge of disease with marked changes in the functional state of its glial cells. One of the most rapid and obvious events is the activation of microglia, the brain’s resident tissue macrophages. Microglial activation is increasingly recognised as an important, early step in the pathophysiological response to traumatic, inflammatory and degenerative tissue changes and even to neoplastic transformation that may affect the nervous system. Microglia react rapidly and in a territorially highly confined way to subtle, acute as well as chronic pathological stimuli. Microglia have been aptly called a “sensor” of pathology in the CNS by Kreutzberg [1,2]. This unique behaviour, which may be due to a lack of gap junctions in these cells [3] is of great practical diagnostic use. Thus, detection of microglial activation provides useful information on formal parameters of disease, such as accurate spatial localisation of the disease process, rate of disease progression and insights into secondary neurodegenerative or adaptive alterations which may take place quite remote from the actual lesion site. Part of the remarkable structural and functional plasticity of microglia is the de novo expression of the “peripheral benzodiazepine binding site" (PBBS). PBBS is linked to important functions, such as immune modulation, steroid synthesis and mitochondrial activity. The PBBS is bound by the isoquinoline, PK11195, which labelled with carbon-11 can be used for positron emission tomography (PET). This opens up a unique window to study glial activity in the living human brain

Microglia in Culture: What Genes Do They Express?

The cell culture model utilized in this study represents one of the most widely used paradigms of microglia in vitro. After 14 days, microglia harvested from the neonatal rat brain are considered ‘mature’. However, it is clear that this represents a somewhat arbitrary definition. In this paper, we provide a transcriptome definition of such microglial cells. More than 7,000 known genes and 1,000 expressed sequence tag clusters were analysed. ‘Microglia genes’ were defined as sequences consistently expressed in all microglia samples tested. Accordingly, 388 genes were identified as microglia genes. Another 1,440 sequences were detected in a subset of the cultures. Genes consistently expressed by microglia included genes known to be involved in the cellular immune response, brain tissue surveillance, microglial migration as well as proliferation. The expression profile reported here provides a baseline against which changes of microglia in vitro can be examined. Importantly, expression profiling of normal microglia will help to provide the presently purely operational definition of ‘microglial activation’ with a molecular biological correlate. Furthermore, the data reported here add to our understanding of microglia biology and allow projections as to what functions microglia may exert in vivo, as well as in vitro

Translating the cellular neuropathology of microglia into neuroimaging results

The brain responds to the challenge of disease with marked changes in the functional state of its glial cells. One of the most rapid and obvious events is the activation of microglia, the brain’s resident tissue macrophages. Microglial activation is increasingly recognised as an important, early step in the pathophysiological response to traumatic, inflammatory and degenerative tissue changes and even to neoplastic transformation that may affect the nervous system. Microglia react rapidly and in a territorially highly confined way to subtle, acute as well as chronic pathological stimuli. Microglia have been aptly called a “sensor” of pathology in the CNS by Kreutzberg [1,2]. This unique behaviour, which may be due to a lack of gap junctions in these cells [3] is of great practical diagnostic use. Thus, detection of microglial activation provides useful information on formal parameters of disease, such as accurate spatial localisation of the disease process, rate of disease progression and insights into secondary neurodegenerative or adaptive alterations which may take place quite remote from the actual lesion site. Part of the remarkable structural and functional plasticity of microglia is the de novo expression of the “peripheral benzodiazepine binding site" (PBBS). PBBS is linked to important functions, such as immune modulation, steroid synthesis and mitochondrial activity. The PBBS is bound by the isoquinoline, PK11195, which labelled with carbon-11 can be used for positron emission tomography (PET). This opens up a unique window to study glial activity in the living human brain