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.
Showing the most recent 10 out of 13 publications
