George H. De Vries - US grants

[unreadable] DESCRIPTION (provided by applicant): Our long-term objective is to determine the axonal factors involved in the failure to remyelinate in diseases such as multiple sclerosis (MS). In the studies proposed here, we will isolate and characterize axonal factors that control the migration, proliferation, and survival of oligodendrocyte precursor cells (OPC cells). We focus on the initial stages of developmental myelination to gain an understanding of the molecular functions and factors that lead to normal development of a myelin sheath. Then we will investigate those same functions and factors in MS brains to determine which factors are inappropriately expressed. We hypothesize that imbalances of axonal-related growth factors contribute to the failure of remyelination in MS. In Specific Aim 1 we will characterize a process by which axonal molecules are released from a membrane fraction enriched in axonal plasma membrane. We will use medium that has been conditioned with OPC cells to stimulate the axonal-enriched fraction. Western blotting will be used to characterize the nature of the axonal factors (e.g., growth factors of different types) that are released from the axonal surface membrane. We will also characterize the types of receptors that have been activated. In Specific Aim 2 we will investigate the influence of axonal factors and how axons regulate migration, proliferation, and survival of OPC cells. Preliminary studies found that solubilized factors can stimulate proliferation. Migration assays using both soluble and particulate fractions will allow us to determine whether axonal contact and/or soluble factors released from axonal membrane are responsible for initiation and cessation of migration and proliferation. Specific Aim 3 directly tests the hypothesis that the axon-oligodendrocyte balance is altered in MS. Demyelinated areas from MS brain will be analyzed for growth factor composition (both type and ratio among them) in order to understand why oligodendrocytes migrate to the demyelinated region, proliferate, but do not remyelinate the demyelinated axons. We will obtain important information about the axonal molecules that control the early events of myelination (i.e. migration, proliferation, and survival of OPC cells), which eventually will enable researchers to pinpoint areas for therapeutic intervention. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Support is requested for the next five annual meetings of the American Society for Neurochemistry beginning with the 2004 meeting to be held in New York City from August 14-18, 2004. To accommodate the breadth of neurochemistry as well as cellular and molecular neurobiology, and to provide in-depth expositions of articular topics, the ASN programs for the next five years will build its scientific program around four interwoven, but distinct, themes. 1) Building the Nervous System: Sessions in this theme address the generation of cell diversity, elaboration of neuronal cytoarchitecture, specificity of synapse formation and the role of growth factors during development. 2) Metabolism and Cell and Molecular Neuroscience: Sessions under this theme deal with basic mechanisms applicable in a wide range of health issues ranging from metabolism to neurotransmitter function and from cell motility to molecular cell structure. 3) Glial Mechanisms and Injury: The crucial role of non-neuronal cells in neural development and pathogenesis are explored in sessions that address basic glial biology and the role of the glia in diseases such as Multiple Sclerosis, Alzheimer's Disease, and CNS injury. 4) Neuronal Degeneration and Disease: This theme continues to be a focus of ASN meetings. Sessions address the mechanisms of Neurodegeneration, the role of inflammation, and the contributions of neurotransmitters to the disease state. These themes have been selected to increase our understanding of the cellular and molecular bases of neural development and disease. NIH support for previous meetings of the ASN has been invaluable for supporting the ASN's scientific programs and for enhancing the ability of ASN to attract graduate students and postdoctoral researchers to attend the meeting.

DESCRIPTION (provided by applicant): Support is requested for the next annual meeting of the American Society for Neurochemistry beginning with the 2005 meeting to be held in Madison, Wisconsin from June 24-29, 2005. To accommodate the breadth of neurochemistry as well as cellular and molecular neurobiology, and to provide in-depth expositions of articular topics, the ASN programs traditionally build its scientific program around 4 interwoven, but distinct, themes. 1. Building the Nervous System: Sessions in this theme address the neurobiology of stem cells, the generation of cell diversity, elaboration of neuronal cytoarchitecture, specificity of synapse formation and the role of growth factors during development. 2. Metabolism and Cell and Molecular Neuroscience: Sessions under this theme deal with basic mechanisms applicable in a wide range of health issues ranging form metabolism to neurotransmitter function and from cell motility to molecular cell structure. 3. Glial Mechanisms and Injury: The crucial role of non-neuronal cells in neural development and pathogenesis are explored in sessions that address basic glial biology and the role of the glia in diseases such as Multiple Sclerosis, Alzheimer's Disease, and CNS injury. 4. Neuronal Degeneration and Disease: This theme continues to be an important focus of ASN meetings. Sessions address the molecular mechanisms of neurodegeneration, the role of inflammation, and the contributions of neurotransmitters to the disease state. These themes have been selected to increase our understanding of the cellular and molecular bases of neural development and disease. NIH support for previous meetings of the ASN has been invaluable for supporting the high quality ASN scientific programs and for making these programs accessible to graduate students, postdoctoral researchers, junior faculty and minorities.