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International Journal of Alzheimer’s Disease
Volume 2010, Article ID 864625, 13 pages
http://dx.doi.org/10.4061/2010/864625
Research Article

Ablation of the Locus Coeruleus Increases Oxidative Stress in Tg-2576 Transgenic but Not Wild-Type Mice

1Biologics Consulting Group, Inc., 400 N. Washington Street, Suite 100, Alexandria, VA 22314, USA
2Department of Medicine, Nursing, and Dentistry, University of Dundee, Nethergate, Dundee DD1 4HN, UK
3Metabolon Inc., 800 Capitola Drive, Suite 1, Durham, NC 27713-4385, USA
4Bayer Cropscience, 3500 Paramount Parkway Morrisville, NC 27560-7218, USA
5Pfizer, 558 Eastern Point Road Groton, CT 06340-5196, USA
6Proteostasis Therapeutics, 200 Technology Square, Suite 402, Boston, MA 02139, USA
7Department of Neuroscience, Duke University, Durham, NC 27708, USA
8Pfizer, Translational Medicine Research Collaboration, Dundee DD1 9SY, UK

Received 24 May 2010; Revised 23 August 2010; Accepted 3 September 2010

Academic Editor: Gemma Casadesus

Copyright © 2010 Orest Hurko et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mice transgenic for production of excessive or mutant forms of beta-amyloid differ from patients with Alzheimer's disease in the degree of inflammation, oxidative damage, and alteration of intermediary metabolism, as well as the paucity or absence of neuronal atrophy and cognitive impairment. Previous observers have suggested that differences in inflammatory response reflect a discrepancy in the state of the locus coeruleus (LC), loss of which is an early change in Alzheimer's disease but which is preserved in the transgenic mice. In this paper, we extend these observations by examining the effects of the LC on markers of oxidative stress and intermediary metabolism. We compare four groups: wild-type or Tg2576 A đť›˝ transgenic mice injected with DSP4 or vehicle. Of greatest interest were metabolites different between ablated and intact transgenics, but not between ablated and intact wild-type animals. The Tg2576_DSP4 mice were distinguished from the other three groups by oxidative stress and altered energy metabolism. These observations provide further support for the hypothesis that Tg2576 A đť›˝ transgenic mice with this ablation may be a more congruent model of Alzheimer's disease than are transgenics with an intact LC.