Date of Award

12-2014

Level of Access Assigned by Author

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biochemistry and Molecular Biology

Advisor

Douglas Currie

Second Committee Member

Stephen Pelsue

Third Committee Member

Xie Hong

Abstract

Human adolescent exposures to arsenic associate with cognitive deficits and when experimental animals are exposed to arsenic behavioral changes occur. Disruption of neuritogenesis during brain development could contribute to these in vivo changes and arsenic is known to disrupt neurite growth in vitro. Neurite growth relies on assembly of the actin and microtubule cytoskeletons. We therefore investigated whether arsenic disrupts these cytoskeletal components as well as proteins that are known to modify cytoskeletal assembly and stabilization. We found that arsenic induces clear disruption of proteins that are critical to neurite growth: actin, Rac1, tubulin, MAP1A, MAP1B, MAP2 and tau. We also present evidence that activation of the RhoA/ROCK pathway contributes to the neurite growth deficit.

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