Date

2017

Department or Program

Neuroscience

Primary Wellesley Thesis Advisor

Deborah Bauer

Additional Advisor(s)

Krystyn J. Van Vliet

Abstract

Oligodendrocytes are specialized glial cells that insulate neuron axons in the central nervous system with a vital proteolipid sheath called myelin. Oligodendrocytes in the adult brain are derived from oligodendrocyte progenitor cells (OPCs), and their differentiation into mature oligodendrocytes can be observed in vitro; however, this process is incomplete as myelin wrapping cannot be observed when there are no physical structures in culture with which developing OPCs can interact. The development of artificial axon surrogates aims to address this problem by developing geometric and mechanical mimics of axons from materials. The work presented here describes the development of a new axon surrogate that incorporates electrical activity into the in vitro platform. Axon surrogates were developed as conductive polymer nanofibers composed of a polyaniline composite, PANI/PG. PANI/PG nanofiber mats fabricated by electrospinning demonstrate unique and dynamic electrical properties that change over the course of the OPC culture. These changes provide evidence that conductive fiber substrata in the future might be used as an indirect method for measuring cell behavior on the mats. Moreover, this myelination detection method could be adjusted for quick and high-throughput readouts, providing an efficient new platform for the drug discovery of remyelination therapies. In addition, when an electrical potential was applied to PANI/PG fiber mats during OPC differentiation, cells showed an upregulation of differentiation and myelination transcripts Hdac11, Cnp, and Mbp 2-4-fold compared to OPCs which did not receive electrical stimulation. These data suggest that developing OPCs are strongly influenced by electric fields.

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