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Access Type

WSU Access

Date of Award

January 2017

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

Anna Moszczynska

Abstract

Methamphetamine (METH) is a widely abused psychostimulant, which can cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes were identified after binge METH exposure, including histone modification, DNA methylation, and changes in miRNA levels. We have shown that binge METH increases expression and activity of Long INterspersed Element (LINE-1), a transposable element, in doublecortin-positive neurons within rat neurogenic zones [1]. The goal of the present study was to identify which type(s) of cells show increases in LINE-1 following binge METH exposure, and determine whether binge METH-induced increases in LINE-1 are associated with cell death. To achieve this goal, male adult Sprague Dawley rats were treated with binge METH (4x 10mg/kg, i.p. every 2 h) or saline, sacrificed 24 hours later, and examined for LINE-1 expression and either markers of cell types in neurogenic zones or signs of apoptosis within the neurogenic zones. We found that increased LINE-1 expression co-localized with most GFAP-positive cells in both the subgranular zone (SGZ) and subventricular zone (SVZ), as well as most NeuN-positive cells in SGZ. We also found that LINE-1 expression co-localized with some, but not all, apoptotic marker expression within the neurogenic zones. However, LINE-1 expression did co-localize with an oxidative stress marker. Collectively, our data suggest that systemic administration of neurotoxic doses of binge METH increases the activity of LINE-1 mostly in glial cells and post-mitotic cells, and may be associated with responses to oxidative stress and/or gliosis.

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