Date of Award

12-2012

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Cindy L. Linn

Second Advisor

Dr. John Jellies

Third Advisor

Dr. John Spitsbergen

Keywords

Excitotoxicity, neuroprotection, retina, glutamate, acetylcholine

Access Setting

Masters Thesis-Open Access

Abstract

Glutamate-induced excitotoxicity has been shown to play a key role in a number of neurodegenerative diseases of the central nervous system. Activation of nicotinic acetylcholine receptors (nAChRs) significantly protects various types of neuronal tissues from excitotoxic cell death (Kaneko et al., 1997; Dajas-Bailador et al., 2000; Wehrwein et al., 2004; Thompson et al., 2006). Tropisetron is a highly selective 5-HT3 class serotonin receptor antagonist that is also a partial acetylcholine (ACh) agonist of the α7 nAChR (Papke et al., 2005). In the current study we aim to determine if tropisetron offers protection to adult pig RGCs. We further aim to determine if protection occurs through activation of α7 nAChRs. We used cell culture methods to isolate adult pig RGCs using the two-step panning technique first described by Wehrwein et al. (2004). Our results show that tropisetron protects adult pig RGCs from glutamate-induced excitotoxicity in a dose-dependent manner. ELISA studies suggest involvement of the p38 MAPK intracellular signaling pathway. Fluorescent immunocytochemistry studies show evidence that receptor internalization occurs during neuroprotection by tropisetron. The results of this study suggest tropisetron warrants further investigation as a therapeutic agent against neurodegenerative disorders involving dysfunction in glutamate activity.

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