The Experts below are selected from a list of 13368 Experts worldwide ranked by ideXlab platform

Huda Akil - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of affymetrix gene chip sensitivity in rat Hippocampal Tissue using sage analysis
    European Journal of Neuroscience, 2002
    Co-Authors: Simon J Evans, Ronald E De Kloet, Nicole A Datson, Mohamed Kabbaj, Robert C Thompson, Erno Vreugdenhil, Stanley J Watson, Huda Akil
    Abstract:

    DNA microarrays are a powerful tool for monitoring thousands of transcript levels simultaneously. However, the use of DNA microarrays in studying the central nervous system faces several challenges. These include the detection of low-abundance transcripts in highly complex Tissue as well as estimating relatively low-magnitude changes in transcript levels in response to experimental manipulation. Many transcripts important to brain function have low expression levels or are expressed in relatively few cells, making them difficult to detect in the complex background of brain Tissue. The aim of the present study is to evaluate the sensitivity of Gene Chip detection of transcripts in brain by using results from serial analysis of gene expression (SAGE) studies. The results of this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably detect medium- to high-abundance transcripts and that detection of low-abundance transcripts, many of which have great relevance to biological function in brain, is inconsistent. Specifically, we estimate that Gene Chips reliably detect no more than 30% of the Hippocampal transcriptome when using a gross Hippocampal dissection as the source Tissue. This report provides the first broad evaluation of Affymetrix Gene Chip sensitivity relevant to studying the brain.

  • review article evaluation of affymetrix gene chip sensitivity in rat Hippocampal Tissue using sage analysis
    2002
    Co-Authors: Simon J Evans, Ronald E De Kloet, Nicole A Datson, Mohamed Kabbaj, Erno Vreugdenhil, Stanley J Watson, Robert Thompson, Huda Akil
    Abstract:

    DNA microarrays are a powerful tool for monitoring thousands of transcript levels simultaneously. However, the use of DNA microarrays in studying the central nervous system faces several challenges. These include the detection of low-abundance transcripts in highly complex Tissue as well as estimating relatively low-magnitude changes in transcript levels in response to experimental manipulation. Many transcripts important to brain function have low expression levels or are expressed in relatively few cells, making them difficult to detect in the complex background of brain Tissue. The aim of the present study is to evaluate the sensitivity of Gene Chip detection of transcripts in brain by using results from serial analysis of gene expression (SAGE) studies. The results of this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably detect medium- to highabundance transcripts and that detection of low-abundance transcripts, many of which have great relevance to biological function in brain, is inconsistent. Specifically, we estimate that Gene Chips reliably detect no more than 30% of the Hippocampal transcriptome when using a gross Hippocampal dissection as the source Tissue. This report provides the first broad evaluation of Affymetrix Gene Chip sensitivity relevant to studying the brain.

Albert J Becker - One of the best experts on this subject based on the ideXlab platform.

  • gene expression variance in Hippocampal Tissue of temporal lobe epilepsy patients corresponds to differential memory performance
    Neurobiology of Disease, 2016
    Co-Authors: Julia Bungenberg, Natascha Surano, Alexander Grote, Rainer Surges, Katharina Pernhorst, Andrea Hofmann, Susanne Schoch, Christoph Helmstaedter, Albert J Becker
    Abstract:

    Abstract Temporal lobe epilepsy (TLE) is a severe brain disorder affecting particularly young adults. TLE is frequently associated with memory deterioration and neuronal damage of the Hippocampal formation. It thereby reveals striking parallels to neurodegenerative disorders including Alzheimer's disease (AD). TLE patients differ with respect to their cognitive performance, but currently little is known about relevant molecular–genetic factors. Here, we correlated differential memory performance of pharmacoresistant TLE patients undergoing neurosurgery for seizure control with in-vitro findings of their Hippocampal Tissues. We analyzed mRNA transcripts and subsequently promoter variants specifically altered in brain Tissue of individuals with ‘very severe’ memory impairment. TLE patients (n = 79) were stratified according to preoperative memory impairment using an established four-tiered grading system ranging from ‘average’ to ‘very severely’. Multimodal cluster analyses revealed molecules specifically associated with synaptic function and abundantly expressed in TLE patients with very impaired memory performance. In a subsequent promoter analysis, we found the single nucleotide polymorphism rs744373 C-allele to be associated with high mRNA levels of bridging integrator 1 (BIN1)/Amphiphysin 2, i.e. a major component of the endocytotic machinery and located in a crucial genetic AD risk locus. Using in vitro luciferase transfection assays, we found that BIN1 promoter activation is genotype dependent and strongly increased by reduced binding of the transcriptional repressor TGIF. Our data indicate that poor memory performance in patients with TLE strongly corresponds to distinctly altered neuronal transcript signatures, which – as demonstrated for BIN1 – can correlate with a particular allelic promoter variant. Our data suggest aberrant transcriptional signaling to significantly impact synaptic dynamics in TLE resulting in impaired memory performance and may serve as basis for future therapy development of this severe comorbidity.

Tatyana Pivneva - One of the best experts on this subject based on the ideXlab platform.

  • maturation of neural stem cells and integration into Hippocampal circuits a functional study in an in situ model of cerebral ischemia
    Journal of Cell Science, 2018
    Co-Authors: Olga Kopach, O A Rybachuk, Volodymyr Krotov, Vitalii Kyryk, Nana Voitenko, Tatyana Pivneva
    Abstract:

    The hippocampus is the most susceptible region of the brain to ischemic lesion, with highly vulnerable pyramidal interneurons to ischemic cell death. A restricted brain neurogenesis limits a withdrawal of massive cell death after stroke that endorses cell-based therapies for neuronal replacement strategies following cerebral ischemia. Neurons differentiated from neural stem/progenitor cells (NSPCs) matured and integrated into host circuitry, improving recovery after stroke. However, how host environment regulates the NSPC behaviour in post-ischemic Tissue remains unknown. Here we studied functional maturation of NSPCs in control and post-ischemic Hippocampal Tissue after modelling cerebral ischemia in situ . We traced maturation of electrophysiological properties and integration of the NSPC-derived neurons into the host circuits, developing appropriate activity that takes 3 weeks or less after engraftment. In the ischemic-injured Tissue, the NSPC-derived neurons exhibited functional deficits and differentiation of embryonic NSPCs was boosted to glial type – oligodendrocytes and astrocytes. Our findings of the delayed neuronal maturation whilst the promoted NSPC differentiation towards glial cell type in post-ischemic conditions provide new insights into stem-cell-therapy for replacement strategies in cerebral ischemia.

Simon J Evans - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of affymetrix gene chip sensitivity in rat Hippocampal Tissue using sage analysis
    European Journal of Neuroscience, 2002
    Co-Authors: Simon J Evans, Ronald E De Kloet, Nicole A Datson, Mohamed Kabbaj, Robert C Thompson, Erno Vreugdenhil, Stanley J Watson, Huda Akil
    Abstract:

    DNA microarrays are a powerful tool for monitoring thousands of transcript levels simultaneously. However, the use of DNA microarrays in studying the central nervous system faces several challenges. These include the detection of low-abundance transcripts in highly complex Tissue as well as estimating relatively low-magnitude changes in transcript levels in response to experimental manipulation. Many transcripts important to brain function have low expression levels or are expressed in relatively few cells, making them difficult to detect in the complex background of brain Tissue. The aim of the present study is to evaluate the sensitivity of Gene Chip detection of transcripts in brain by using results from serial analysis of gene expression (SAGE) studies. The results of this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably detect medium- to high-abundance transcripts and that detection of low-abundance transcripts, many of which have great relevance to biological function in brain, is inconsistent. Specifically, we estimate that Gene Chips reliably detect no more than 30% of the Hippocampal transcriptome when using a gross Hippocampal dissection as the source Tissue. This report provides the first broad evaluation of Affymetrix Gene Chip sensitivity relevant to studying the brain.

  • review article evaluation of affymetrix gene chip sensitivity in rat Hippocampal Tissue using sage analysis
    2002
    Co-Authors: Simon J Evans, Ronald E De Kloet, Nicole A Datson, Mohamed Kabbaj, Erno Vreugdenhil, Stanley J Watson, Robert Thompson, Huda Akil
    Abstract:

    DNA microarrays are a powerful tool for monitoring thousands of transcript levels simultaneously. However, the use of DNA microarrays in studying the central nervous system faces several challenges. These include the detection of low-abundance transcripts in highly complex Tissue as well as estimating relatively low-magnitude changes in transcript levels in response to experimental manipulation. Many transcripts important to brain function have low expression levels or are expressed in relatively few cells, making them difficult to detect in the complex background of brain Tissue. The aim of the present study is to evaluate the sensitivity of Gene Chip detection of transcripts in brain by using results from serial analysis of gene expression (SAGE) studies. The results of this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably detect medium- to highabundance transcripts and that detection of low-abundance transcripts, many of which have great relevance to biological function in brain, is inconsistent. Specifically, we estimate that Gene Chips reliably detect no more than 30% of the Hippocampal transcriptome when using a gross Hippocampal dissection as the source Tissue. This report provides the first broad evaluation of Affymetrix Gene Chip sensitivity relevant to studying the brain.

Julia Bungenberg - One of the best experts on this subject based on the ideXlab platform.

  • gene expression variance in Hippocampal Tissue of temporal lobe epilepsy patients corresponds to differential memory performance
    Neurobiology of Disease, 2016
    Co-Authors: Julia Bungenberg, Natascha Surano, Alexander Grote, Rainer Surges, Katharina Pernhorst, Andrea Hofmann, Susanne Schoch, Christoph Helmstaedter, Albert J Becker
    Abstract:

    Abstract Temporal lobe epilepsy (TLE) is a severe brain disorder affecting particularly young adults. TLE is frequently associated with memory deterioration and neuronal damage of the Hippocampal formation. It thereby reveals striking parallels to neurodegenerative disorders including Alzheimer's disease (AD). TLE patients differ with respect to their cognitive performance, but currently little is known about relevant molecular–genetic factors. Here, we correlated differential memory performance of pharmacoresistant TLE patients undergoing neurosurgery for seizure control with in-vitro findings of their Hippocampal Tissues. We analyzed mRNA transcripts and subsequently promoter variants specifically altered in brain Tissue of individuals with ‘very severe’ memory impairment. TLE patients (n = 79) were stratified according to preoperative memory impairment using an established four-tiered grading system ranging from ‘average’ to ‘very severely’. Multimodal cluster analyses revealed molecules specifically associated with synaptic function and abundantly expressed in TLE patients with very impaired memory performance. In a subsequent promoter analysis, we found the single nucleotide polymorphism rs744373 C-allele to be associated with high mRNA levels of bridging integrator 1 (BIN1)/Amphiphysin 2, i.e. a major component of the endocytotic machinery and located in a crucial genetic AD risk locus. Using in vitro luciferase transfection assays, we found that BIN1 promoter activation is genotype dependent and strongly increased by reduced binding of the transcriptional repressor TGIF. Our data indicate that poor memory performance in patients with TLE strongly corresponds to distinctly altered neuronal transcript signatures, which – as demonstrated for BIN1 – can correlate with a particular allelic promoter variant. Our data suggest aberrant transcriptional signaling to significantly impact synaptic dynamics in TLE resulting in impaired memory performance and may serve as basis for future therapy development of this severe comorbidity.