The Role of AlphaB-crystallin During Peripheral Nerve Regeneration

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atmire.migration.oldid4775
dc.contributor.advisorOusman, Shalina
dc.contributor.authorLim, Erin-Mai
dc.contributor.committeememberZochodne, Douglas
dc.contributor.committeememberBiernaskie, Jeff
dc.contributor.committeememberMidha, Rajiv
dc.contributor.committeememberLacroix, Steve
dc.date.accessioned2016-10-17T16:33:46Z
dc.date.available2016-10-17T16:33:46Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractThis dissertation characterizes the role of a small heat shock protein called alphaB-crystallin (αBC) in peripheral nerve regeneration. Peripheral nerve injuries are fairly common and often result in patient disability due to the partial and incomplete regeneration of nerves. The expression of αBC in the peripheral nervous system (PNS) has been known, but its role has not been determined. Because many protective and beneficial functions of the heat shock protein has been reported in a variety of cells and models, I explored whether αBC also has a beneficial role in the PNS particularly after sustaining an injury. Using 129S6 wild-type (WT) and αBC null (αBC-/-) mice, I discovered that αBC positively influenced PNS regeneration. Following sciatic nerve crush, I found that αBC-/- mice had decreased functional recovery, slower motor nerve conduction velocities, and thinner myelin sheaths 28 days post-injury. I additionally observed higher numbers of macrophages (mΦ) in the distal sciatic nerves of αBC-/- mice during the late time points post-injury that may explain the heightened sensitivity towards mechanical and thermal stimulation observed in these animals. I further elucidated that the injury deficits observed in the αBC-/- mice were due to aberrant neuregulin-1/ErbB2 and pAkt signaling. Cumulatively, these findings indicate that αBC positively modulates peripheral nerve regeneration by promoting remyelination and mediating clearance of macrophages in the distal nerve. Lastly, because of reduced expression of αBC with increasing age, I investigated whether αBC plays a role in deficits associated with the aging PNS. I found that αBC-/- mice displayed thinner myelin sheaths before and after injury at different ages. Moreover, 12-month-old αBC-/- mice displayed higher numbers of macrophages before and after injury and, lower numbers of squalene monooxygenase (SQLE), an important enzyme in cholesterol synthesis. These findings are consistent with previous reports that revealed in the aging PNS there is upregulation of genes associated with inflammation and downregulation of genes associated with lipid metabolism. Further exploration is needed to identify the mechanisms involved. Collectively, the work presented in this dissertation provides novel evidence of the significant roles of αBC following peripheral nerve injury.en_US
dc.identifier.citationLim, E. (2016). The Role of AlphaB-crystallin During Peripheral Nerve Regeneration (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/28318en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/28318
dc.identifier.urihttp://hdl.handle.net/11023/3434
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectNeuroscience
dc.subject.classificationPeripheral Nervous Systemen_US
dc.subject.classificationRegenerationen_US
dc.subject.classificationHeat Shock Proteinen_US
dc.subject.classificationWallerian degenerationen_US
dc.subject.classificationCrystallinen_US
dc.titleThe Role of AlphaB-crystallin During Peripheral Nerve Regeneration
dc.typedoctoral thesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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