Early Intervention with a Multi-Ingredient Dietary Supplement Improves Mood and Spatial Memory in a Triple Transgenic Mouse Model of Alzheimer’s Disease

Article type: Research Article

Authors: Hutton, Craig P.^a | Lemon, Jennifer A.^b | Sakic, Boris^c | Rollo, C. David^b | Boreham, Douglas R.^b | Fahnestock, Margaret^c | Wojtowicz, J. Martin^d | Becker, Suzanna^{a; *}

Affiliations: [a] Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, ON, Canada | [b] Department of Biology, McMaster University, Hamilton, ON, Canada | [c] Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada | [d] Department of Physiology, University of Toronto, Toronto, ON, Canada

Correspondence: [*] Correspondence to: Suzanna Becker, Department of Psychology, Neuroscience & Behaviour, Psychology Building, Room 312, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8S 4K1, Canada. Tel.: +1 905 525 9140/Ext. 23020; Fax: +1 905 529 6225; E-mail: [email protected].

Abstract: The increasing global burden of Alzheimer’s disease (AD) and failure of conventional treatments to stop neurodegeneration necessitates an alternative approach. Evidence of inflammation, mitochondrial dysfunction, and oxidative stress prior to the accumulation of amyloid-β in the prodromal stage of AD (mild cognitive impairment; MCI) suggests that early interventions which counteract these features, such as dietary supplements, may ameliorate the onset of MCI-like behavioral symptoms. We administered a polyphenol-containing multiple ingredient dietary supplement (MDS), or vehicle, to both sexes of triple transgenic (3xTg-AD) mice and wildtype mice for 2 months from 2–4 months of age. We hypothesized that the MDS would preserve spatial learning, which is known to be impaired in untreated 3xTg-AD mice by 4 months of age. Behavioral phenotyping of animals was done at 1-2 and 3-4 months of age using a comprehensive battery of tests. As previously reported in males, both sexes of 3xTg-AD mice exhibited increased anxiety-like behavior at 1-2 months of age, prior to deficits in learning and memory, which did not appear until 3-4 months of age. The MDS did not reduce this anxiety or prevent impairments in novel object recognition (both sexes) or on the water maze probe trial (females only). Strikingly, the MDS specifically prevented 3xTg-AD mice (both sexes) from developing impairments (exhibited by untreated 3xTg-AD controls) in working memory and spatial learning. The MDS also increased sucrose preference, an indicator of hedonic tone. These data show that the MDS can prevent some, but not all, psychopathology in an AD model.

Keywords: Alzheimer’s disease, anhedonia, anxiety, dietary supplements, learning, memory, mice, mild cognitive impairment, reversal learning, transgenic, working memory

DOI: 10.3233/JAD-170921

Journal: Journal of Alzheimer's Disease, vol. 64, no. 3, pp. 835-857, 2018