Improved Spatial Learning Strategy and Memory in Aged Alzheimer AβPPswe/PS1dE9 Mice on a Multi-Nutrient Diet

Article type: Research Article

Authors: Wiesmann, Maximilian^a | Jansen, Diane^a | Zerbi, Valerio^a | Broersen, Laus M.^b | Garthe, Alexander^c | Kiliaan, Amanda J.^{a; *}

Affiliations: [a] Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience (Department: Anatomy), Nijmegen, The Netherlands | [b] Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands | [c] DZNE – German Center for Neurodegenerative Diseases, Standort Dresden, Dresden, Germany

Correspondence: [*] Correspondence to: Amanda J. Kiliaan, PhD, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Center for Neuroscience (Department: Anatomy), PO BOX 9101, 6500HB Nijmegen, The Netherlands. Tel.: +31 24 3614378; Fax: +31 24 3613789; E-mail: [email protected].

Abstract: There is accumulating evidence showing that lifestyle factors like diet may influence the onset and progression of Alzheimer's disease (AD). Our previous studies suggest that a multi-nutrient diet, Fortasyn, containing nutritional precursors and cofactors for membrane synthesis, viz. docosahexaenoic acid, eicosapentaenoic acid, uridine-mono-phosphate, choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium, has an ameliorating effect on cognitive deficits in an AD mouse model. In the present study we analyzed learning strategies and memory of 11-month-old AβPPswe/PS1dE9 (AβPP/PS1) mice in the Morris water maze (MWM) task performed after nine months of dietary intervention with a control diet or a Fortasyn diet to characterize diet-induced changes in cognitive performance. The Fortasyn diet had no significant effect on MWM task acquisition. To assess hippocampus-dependent learning, the strategies that the mice used to find the hidden platform in the MWM were analyzed using the swim path data. During the fourth day of the MWM, AβPP/PS1 mice on control diet more often used the non-spatial random search strategy, while on the Fortasyn diet, the transgenic animals exhibited more chaining strategy than their wild-type littermates. During the probe trial, AβPP/PS1 mice displayed no clear preference for the target quadrant. Notably, in both transgenic and nontransgenic mice on Fortasyn diet, the latency to reach the former platform position was decreased compared to mice on the control diet. In conclusion, this specific nutrient combination showed a tendency to improve searching behavior in AβPP/PS1 mice by increasing the use of a more efficient search strategy and improving their swim efficiency by decreasing the latency to reach the former platform position.

Keywords: Alzheimer's disease, cognition, docosahexaenoic acids, learning, memory, transgenic mice

DOI: 10.3233/JAD-130179

Journal: Journal of Alzheimer's Disease, vol. 37, no. 1, pp. 233-245, 2013