Affiliations: [a] Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [b] Center for Health and Disease Research, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [c] Department of Biological Sciences, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [d] Department of Biochemistry, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [e] Department of Health and Clinical Science, University of Massachusetts, Lowell, Lowell, MA 01854, USA | [f] Nutrix Corporation/AST Products, Billerica, MA 01821, USA
Correspondence:
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Corresponding author: T.B. Shea, Center for Cellular Neurobiology and Neurodegeneration Research, Departments of Biological Sciences, University of Massachusetts, Lowell, Lowell, MA 01854, USA. Tel.: +1 978 934 2881; Fax: +1 978 934 3044; E-mail: Thomas_Shea@uml.edu.
Abstract: Compensatory upregulation in endogenous antioxidants has been shown to accompany certain genetic and dietary deficiencies that promote oxidative stress, including that related to Alzheimer's disease. We compared antioxidant levels in brain tissue of normal and transgenic mice lacking apolipoprotein E following dietary deprivation of vitamin E or folate. As described previously, ApoE-deficient mice displayed increased levels of the endogenous antioxidant glutathione as compared to normal mice, and increased these levels further following folate deprivation. By contrast, glutathione was depleted following vitamin E deprivation in brain tissue of normal and ApoE-deficient mice. TBAR analyses confirmed increased oxidative damage following vitamin E deprivation. However, combined deprivation of folate and vitamin E resulted in levels of glutathione intermediate between those observed following deprivation of either agent, indicating that the lack of compensatory increase in glutathione following vitamin E deprivation was not due to overt neurotoxicity. Similar results were observed for total antioxidant levels in brain tissue. The differential response to vitamin E and folate deprivation is consistent with the possibility that specific differences in oxidative damage may result from deficiencies in either of these agents. The lack of a compensatory response to vitamin E deprivation highlights the importance of dietary vitamin E in prevention of chronic neurodegeneration.
