The effect of the selective estrogen receptor modulator LY117018 on peripheral nerve regeneration / by Roger J. McMurray.

Author/creator McMurray, Roger J. author.
Other author Kalmus, Gerhard W., degree supervisor.
Other author Murashov, Alexander K., degree supervisor.
Other author East Carolina University. Department of Biology.
Format Theses and dissertations
Production2003.
Descriptionxv, 112 leaves : illustrations (some color) ; 28 cm
Supplemental ContentAccess via ScholarShip
Subjects

Summary The aim of this study was to examine the effects of LY117018, a selective estrogen receptor modulator, on peripheral nerve regeneration, using a model of sciatic nerve crush injury in mice. Sciatic functional index, an index of functional recovery, was significantly higher in LY117018 treated mice throughout regeneration. Semi-thin sections revealed a significant increase in the total number of regenerating nerve fibers at day 7, and the mean axonal area of myelinated fibers at 7, 14, and 21 days after injury, in LY117018 treated mice. Immunohistochemistry revealed estrogen receptor-[alpha] and estrogen receptor-[beta] proteins localized in lumbar motor neurons. Quantitative real-time RT-PCR demonstrated an upregulation of estrogen receptors-[alpha] and -[beta] mRNA on the injured side of the lumbar spinal cord. Immunohistochemistry showed positive staining for estrogen receptor-[alpha] and -[beta], and extracellular signal-regulated kinase (ERK) in the axons of the sciatic nerve. Western blot confirmed the presence of these proteins in the nerve axons. Analysis of axonal transport through retrograde labeling of motor neurons showed that LY117018 potentiated axonal transport, while ICl 182,780 (inhibitor of estrogen receptors) and U0126 (inhibitor of ERK) blocked the action of LY117018, delineating estrogen receptors and ERK as its possible targets. These findings indicate that LY117018 markedly accelerated peripheral nerve regeneration and functional recovery, possibly via estrogen receptors and activation of the ERK signaling pathway.
General notePresented to the faculty of the Department of Biology.
General noteAdvisor: Gerhard W. Kalmus
General noteAdvisor: Alexander K. Murashov
Dissertation noteM.S. East Carolina University 2003
Bibliography noteIncludes bibliographical references (leaves 93-97).
Genre/formAcademic theses.
Genre/formAcademic theses.
Genre/formThèses et écrits académiques.

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