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Title page for ETD etd-10132014-160147


Type of Document Dissertation
Author Ho, Karen W.
URN etd-10132014-160147
Title The Transient Receptor Potential Vanilloid-1 Channel in Stress-Induced Astrocyte Migration
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
Gregg Stanwood Committee Chair
Bruce Carter Committee Member
David Calkins Committee Member
Kevin Currie Committee Member
Rebecca Sappington Committee Member
Vsevolod Gurevich Committee Member
Keywords
  • astrocyte
  • migration
  • TRPV1
Date of Defense 2014-08-19
Availability unrestricted
Abstract
Astrocytes are one type of glia in the central nervous system, and they provide metabolic and structural support to neurons. Following injury astrocytes undergo an injury stress response known as reactive gliosis. Gliosis is characterized by both morphological and functional changes including increased cell migration. Astrocyte migration is seen in multiple disease states including glaucoma, age-related macular degeneration and glial scar formation. Migration relies upon multiple signaling pathways, many of which are activated by increases in calcium. One such source of calcium influx is the transient receptor potential vanilloid 1 (TRPV1) channel, which has a high calcium conductance and is expressed by astrocytes. Using a wound healing model, I found that antagonism of TRPV1 reduced both astrocyte migration and calcium influx following injury. Increases in calcium can drive cytoskeletal remodeling to facilitate migration, and I found that TRPV1 antagonism reduced alpha-tubulin intensity and induced retraction of both actin and alpha-tubulin in astrocytes following injury. My results suggest that in astrocytes TRPV1 is activated by injury, and that this activation contributes to injury-induced migration through an influx of calcium and subsequent cytoskeletal remodeling. By better understanding the events that underlie astrocyte migration, we can target astrocyte reactivity and migration to promote neuronal survival.

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