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      • HARVEST
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      Mechanisms controlling the cell body response to axon injury in dorsal root ganglion neurons

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      Rasheed_Thesis.pdf (5.635Mb)
      Date
      2010
      Author
      Bani Hammad, Rasheed Ahmed
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
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      Abstract
      Successful axon regeneration appears to depend on the development of an injury response. Dorsal root ganglion neurons exemplify the necessity of this injury response in a unique way. Peripheral nerve transection leads to development of an injury response and successful regeneration whereas central root transection does neither. The injury response may involve extracellular and intracellular pathways. To investigate the extraneuronal influences, we performed nerve transection of either the central or peripheral axon branches and studied the expression of GAP-43, a key growth associated protein, and the transcription factors ATF3, c-Jun, and STAT3. Our results show that the responses to peripheral versus central nerve transection are fundamentally different. Peripheral but not central nerve transection increases GAP-43, ATF3, and c-Jun expression. STAT3, however, is upregulated as a result of central but not peripheral nerve transection. To investigate potential intracellular signalling pathways, we applied FGF-2, an extracellular mitogen, or an analog of cAMP, an intracellular second messenger to the cut end of the peripheral axon. Our results indicate that FGF-2 and cAMP act as activators of GAP-43 expression. On the other hand, FGF-2 and cAMP act to downregulate the expression of ATF3. FGF-2 upregulates c-Jun and the activated form of STAT3. Paradoxically, the regulation of GAP-43 expression by cAMP or by FGF-2 in vivo shows opposing results from the previously reported in vitro studies. Our present results suggest that the peripheral nerve injury response may be governed by at least three different signalling pathways.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Anatomy and Cell Biology
      Program
      Anatomy and Cell Biology
      Supervisor
      Schreyer, David J.S.
      Copyright Date
      2010
      URI
      http://hdl.handle.net/10388/etd-05102010-172114
      Subject
      STAT3
      ATF3
      cAMP
      GAP-43
      transcription factors
      peripheral nerve injury
      transection
      dorsal root ganglion
      sensory neurons
      FGF-2
      c-Jun
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      • Graduate Theses and Dissertations
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