Date of Graduation

Fall 2009

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul L. Durham

Abstract

Release of calcitonin gene-related peptide (CGRP) from trigeminal sensory nerves is implicated in the underlying pathology of migraine. While the therapeutic benefits of grape seed extract (GSE) to inhibit pathophysiological mechanisms associated with cardiovascular disease are well known, the potential benefit of GSE to decrease neurogenic inflammation has not been investigated. The goal of my study was to determine whether GSE could inhibit CGRP expression in primary cultures of trigeminal ganglion neurons as well as a human cell line, DMS 153 cells. CGRP was significantly increased in primary rat trigeminal ganglia cultures in response to a depolarizing stimulus by KCl or capsaicin. Pretreatment with GSE repressed stimulated release of CGRP from trigeminal ganglion neurons. Similarly, GSE repressed stimulated human CGRP promoter activity and mitogen activated protein kinases (MAPK) reporter genes in DMS 153 cells. Moreover, overnight treatment with GSE suppressed basal human CGRP promoter activity. These data provide evidence that GSE can inhibit stimulated and unstimulated CGRP synthesis and secretion from neuronal cells and repress MAP kinase pathways in in vitro-cultured mammalian cells. Furthermore, this study validates the use of primary trigeminal ganglion neuronal cultures and the human cell-line DMS 153 as cellular models for screening plant-based compounds for inhibitory effects on CGRP gene expression.

Keywords

CGPR, grape seed, MAPK, migraine, TMJ, trigeminal, inflammation

Subject Categories

Biology

Copyright

© Amanda C. Herbster

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