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Degree

Doctor of Philosophy, Case Western Reserve University, Neurosciences, 2004.

Abstract

Sensory neurons of the dorsal root ganglia (DRG) are essential for successful healing of injured skin. Neuropeptides such as calcitonin gene-related peptide (CGRP) are released centrally in response to a skin injury to induce pain sensation and are also released at the site of injury to induce vasodilation. The Transforming Growth Factor β superfamily member Activin has been proposed to regulate sensory neuropeptide expression during development, but its role in adult DRG neurons is not known. The studies in this thesis focus on a role for activin in modulation of CGRP expression after a skin injury. Although activin is expressed in low levels in normal adult skin, it is elevated in the skin wound margin two days after wounding. CGRP expression is also increased in cutaneous neurons that innervate the wound site. Activin increases CGRP expression in adult DRG neuron in vitro, which suggests that adult neurons are still plastic and are capable of responding to activin with increased CGRP expression. Activin signals through Smad2 in adult neurons, and in vitro isolation of neurites from cell bodies through the use of compartmented cultures suggests that activin signaling at nerve terminals activates Smad2 in cell bodies. Pilot data also suggest that activin is retrogradely transported in vivo, suggesting a model of transport of the activin signal. In addition to an acute skin wound, the chronic skin disease psoriasis was examined for activin expression. Activin is elevated in psoriatic skin and is highly expressed in proliferating skin cells, while activated Smad2 is detectable in differentiating skin cells, suggesting a role for activin in skin differentiation in psoriasis. Taken together, these data support the hypothesis that skin-derived activin modulates neuropeptide expression after a skin injury in order to promote wound healing.

Subject Headings

Biology, Neuroscience

Keywords

activin; sensory neurons; calcitonin gene-related peptide; skin wound; dorsal root ganglion; psoriasis; nerve growth factor

Advisor

Alison K Hall

Pages

213p.

Document number: case1089320174
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=case1089320174

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