Beneficial Effects of Dietary EGCG and Voluntary Exercise on Behavior in an Alzheimer's Disease Mouse Model

Article type: Research Article

Authors: Walker, Jennifer M.^a | Klakotskaia, Diana^a | Ajit, Deepa^{b; d} | Weisman, Gary A.^{b; d} | Wood, W. Gibson^f | Sun, Grace Y.^{b; c; e} | Serfozo, Peter^b | Simonyi, Agnes^{b; e} | Schachtman, Todd R.^{a; *}

Affiliations: [a] Department of Psychological Sciences, University of Missouri, Columbia, MO, USA | [b] Department of Biochemistry, University of Missouri, Columbia, MO, USA | [c] Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA | [d] Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA | [e] Center for Translational Neuroscience, University of Missouri, Columbia, MO, USA | [f] Department of Pharmacology, University of Minnesota, Geriatric Research Education and Clinical Center, VAMC, Minneapolis, MN, USA

Correspondence: [*] Correspondence to: Todd R. Schachtman, Department of Psychological Sciences, 210 McAlester Hall, University of Missouri, Columbia, MO 65211, USA. Tel.: +1 573 882 3154; Fax: +1 573 882 7710; E-mail: Schachtmant@missouri.edu.

Abstract: Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. The present study investigated the effects of 4 months of wheel-running exercise, initiated at 2-months of age, in conjunction with the effects of the green tea catechin (-)-epigallocatechin-3-gallate (EGCG) administered orally in the drinking water (50 mg/kg daily) on: 1) behavioral measures: learning and memory performance in the Barnes maze, nest building, open-field, anxiety in the light-dark box; and 2) soluble amyloid-β (Aβ) levels in the cortex and hippocampus in TgCRND8 (Tg) mice. Untreated Tg mice showed hyperactivity, relatively poor nest building behaviors, and deficits in spatial learning in the Barnes maze. Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble Aβ1-42 levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.

Keywords: AβPP transgenic mice, Alzheimer's disease, behavior, exercise, EGCG, learning

DOI: 10.3233/JAD-140981

Journal: Journal of Alzheimer's Disease, vol. 44, no. 2, pp. 561-572, 2015