Date of Award

1-1-2010

Document Type

Thesis

Degree Name

M.S.

Department

Biological Sciences

First Advisor

Daniel A. Linseman

Keywords

apoptosis, mitochondrial oxidative stress, neuronal death, nutraceutical antioxidants

Abstract

Neurodegenerative diseases such as Parkinson's and amyotrophic lateral sclerosis have devastating consequences to the afflicted patients. A major cellular pathophysiology underlying these diseases is mitochondrial oxidative stress (MOS) leading to neuronal death. Here, we investigated the neuroprotective effects of a novel class of nutraceuticals, anthocyanins, against MOS-induced death in primary cultures of rat cerebellar granule neurons (CGNs). Anthocyanins are natural antioxidants whose neuroprotective potential has yet to be examined in detail. Kuromanin and callistephin are anthocyanins derived from black rice and strawberries, respectively. Glutathione (GSH)-sensitive MOS and intrinsic apoptosis were induced in CGNs by the Bcl-2 inhibitor, HA14-1. Callistephin and kuromanin each demonstrated significant neuroprotection from this MOS-induced death that was equal to that provided by the green tea polyphenol, epigallocatechin 3-gallate; however, neither anthocyanin was as effective as GSH at rescuing CGNs. Incubation with HA14-1 alone resulted in nearly 90% apoptosis of CGNs and either callistephin or kuromanin reduced this effect to approximately 20% cell death. Treatment with HA14-1 caused a marked depletion of mitochondrial GSH in CGNs to approximately 40% of the control level. Callistephin and kuromanin essentially prevented the reduction in this critical pool of endogenous antioxidant. These data indicate that callistephin and kuromanin represent a new class of neuroprotective compounds that warrant further study as possible therapeutic agents for the treatment of neurodegenerative diseases caused by MOS.

Provenance

Recieved from ProQuest

Rights holder

Natalie Anne Kelsey

File size

69 p.

File format

application/pdf

Language

en

Discipline

Neurosciences

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