Protective Effects of Dietary Supplementation with a Combination of Nutrients in a Transgenic Mouse Model of Alzheimer's Disease

Abstract

Objective: This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer's disease (AD).

Methods: A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain.

Results: An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the β-amyloid1-42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice.

Conclusions: Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. The possible mechanisms of action of compound nutrients.

Ach: acetylcholine; cAMP: Cycilic adenosine monophospate; APP: amyloid precursor protein-presenilin; Aβ: anti-β-amyloid; GSH-PX: glutathione peroxidase; SOD: superoxide dismutase; TChE: total cholinesterase.

Fig 2. The trend of the average weights of the four groups.

Fig 3. Trajectories of mice in the Morris water maze tests.

Fig 4. Results from Morris water maze tests.

(A) The average incubation period from the first to fifth day for the four groups. After 3 months and 7 months of intervention, the mice in HG and NG spent much less time searching for new (reversal) hidden platform on each reversal training day compared to MG, * P

Fig 5. Immunofluorescence staining with rabbit anti-Aβ1–42 and HE dyeing of the temporal cortex and hippocampus of APP/PSN mice.

(1) LG and HG: APP/PSN (Fig 5A) mice with 7 months of intervention; MG: APP/PSN (Fig 5B) mice without intervention and their wild-type littermates (NG). (2) LG and HG: ±, MG: +++, NG:–(Fig 5C and 5D).