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Astrocyte proteoglycans in a model of reactive gliosis

Hoke, Ahmet
http://rave.ohiolink.edu/etdc/view?acc_num=case1057944965

Abstract Details

1994, Doctor of Philosophy, Case Western Reserve University, Neuroscience and Bioengineering.
Since the time of Ramon y Cajal, reactive gliosis has been considered to be a major element in the failure of axons to regenerate in the mature mammalian central nervous system. Molecular components of injured tissue associated with reactive glial cells are now being uncovered. In order to study the extracellular matrix constituents associated with reactive astrocytes, we developed an in vitro model of glial reactivity. This model was based on the observation that regions of increased gliosis surround deposits of beta amyloid peptide (βAP) in senile plaques of Alzheimer's disease. In this model, substrate-bound βAP induced a reactive state in cortical and hippocampal but not cerebellar and spinal cord astrocytes. This reactivity was associated with morphological and motility changes as well as alterations in the proteoglycan metabolism in astrocytes. There was increased synthesis and matrix deposition of a specific hybrid proteoglycan containing both chondroitin sulfate and heparan sulfate glycosaminoglycan chains. This proteoglycan, synthesized by reactive astrocytes was partially purified and shown to be repulsive to neurite outgrowth from embryonic retinal explants. Its inhibitory properties were largely attributable to the presence of chondroitin sulfate chains. I believe this is the first identification of a proteoglycan with neurite inhibitory properties associated with reactive astrocytes. This proteoglycan, and perhaps others like it, in concert with additional elements in the extracellular matrix may play an important role in the failure of regeneration following injury in the adult mammalian central nervous system. These findings also suggest that specific molecular triggers of functionally inhibitory gliosis may exist in the CNS and that astrocytes are regionally heterogenous in their reactive response to gliotic triggers like βAP. Heterogeneity in interactions between βAP and surrounding astrocytes may play a role in the region-specific pathogenesis of Alzheimer's disease.
Jerry Silver (Advisor)
121 p.
Biology, Neuroscience
Astrocyte proteoglycans model reactive gliosis

Recommended Citations

Citations

  • Hoke, A. (1994). Astrocyte proteoglycans in a model of reactive gliosis [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1057944965

    APA Style (7th edition)

  • Hoke, Ahmet. Astrocyte proteoglycans in a model of reactive gliosis. 1994. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1057944965.

    MLA Style (8th edition)

  • Hoke, Ahmet. "Astrocyte proteoglycans in a model of reactive gliosis." Doctoral dissertation, Case Western Reserve University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1057944965

    Chicago Manual of Style (17th edition)

case1057944965
447
© 1994, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.