The proposed investigations are designed to identify environmental factors that support axon growth during experimentally induced axon tract formation in the developing mammalian CNS, and to determine if those, or similar factors can be implicated in the failure of regeneration in adult animals. In earlier studies we have shown that nitrocellulose implants coated principally with astrocytes from young animals are able to support axon growth in neonates, and when transplanted, suppress scar formation and promise directed axon growth in the mature mouse forebrain. Implants coated with astrocytes from mature animals fail to support axon growth in either developing or mature animals. To identify the cellular and molecular properties of purified astrocytes important in the support of axonal growth, we will first purify astrocytes from implants of different ages, and compare the capacity of young against old astrocytes to support axonal elongation """"""""in vitro"""""""". Second, we will assess whether this change from young to old is an intrinsic property of the astrocytes or depends on environmental factors. Third, we will determine if astrocytes preferentially support axonal growth from neurons of the same, rather than remote regions of the brain. Fourth, monoclonal antibodies will be generated that distinguish between young and old astrocytes; and used to influence axonal growth on astrocytes """"""""in vitro"""""""", will be used to investigate the molecular basis of the axon/astrocyte interaction through biochemical characterization of their antigens. These studies will provide a better understanding of the role of astroglia in the regulation of CNS axonal growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025597-05
Application #
3410873
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-02-01
Project End
1993-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Zhang, H; Miller, R H (1996) Density-dependent feedback inhibition of oligodendrocyte precursor expansion. J Neurosci 16:6886-95
Zhang, H; Miller, R H (1995) Asynchronous differentiation of clonally related spinal cord oligodendrocytes. Mol Cell Neurosci 6:16-31
Maier, C E; Miller, R H (1995) Development of glial cytoarchitecture in the frog spinal cord. Dev Neurosci 17:149-59
Zhou, L; Szigeti, V; Miller, R H (1995) Characterization of a novel oligodendrocyte cell surface molecule. J Neurosci Res 42:504-15
Fok-Seang, J; Miller, R H (1994) Distribution and differentiation of A2B5+ glial precursors in the developing rat spinal cord. J Neurosci Res 37:219-35
Smith, G M; Jacobberger, J W; Miller, R H (1993) Modulation of adhesion molecule expression on rat cortical astrocytes during maturation. J Neurochem 60:1453-66
Szigeti, V; Miller, R H (1993) A cell surface antigen expressed by astrocytes and their precursors. Glia 8:20-32
Gillaspy, G E; Miller, R H; Samols, D et al. (1993) Antigenic and differentiative heterogeneity among human glioblastomas. Cancer Lett 68:215-24
Zhang, H; Miller, R H; Rutishauser, U (1992) Polysialic acid is required for optimal growth of axons on a neuronal substrate. J Neurosci 12:3107-14
Fok-Seang, J; Miller, R H (1992) Astrocyte precursors in neonatal rat spinal cord cultures. J Neurosci 12:2751-64

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