Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high fat diet

Authors: CAREY, AMANDA - Simmons College; GILDAWIE, KELSEA - Simmons College; ROVNAK, ABIGAIL - Simmons College; Thangthaeng, Nopporn; Fisher, Derek; Shukitt-Hale, Barbara

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/2017
Publication Date: 9/21/2017
Publication URL: http://handle.nal.usda.gov/10113/5883113
Citation: Carey, A.N., Gildawie, K.R., Rovnak, A., Thangthaeng, N., Fisher, D.R., Shukitt Hale, B. 2017. Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high fat diet. Nutritional Neuroscience. https://doi.org/10.1080/1028415X.2017.1411875.
DOI: https://doi.org/10.1080/1028415X.2017.1411875

Interpretive Summary: It was previously demonstrated that middle-aged mice fed a high-fat diet (HFD) had impaired memory, and that supplementation of HFD with blueberry reduced these memory deficits. As a follow-up to that study, brain tissue from HFD-fed mice with and without blueberry supplementation was examined to determine the cellular mechanism(s) by which blueberry protected the brain from memory impairments associated with HFD. Results showed a significant decrease in the number of inflammatory brain cells in mice fed HFD + blueberry compared to mice fed HFD alone. Mice fed HFD + blueberry had higher levels of chemical and cellular indicators of normal brain cell function, in the area of the brain involved in memory, than mice fed HFD alone. Therefore, this study demonstrates that supplementation of a HFD with blueberry reduces brain inflammation and increases normal brain function, and suggests that these changes mediate blueberry’s protection against memory deficits in HFD-fed mice.

Technical Abstract: Objectives: Consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. Blueberries may prevent and even reverse age-related alterations in neurochemistry and behavior. It was previously demonstrated that middle-aged mice fed HFD had impaired memory; however supplementation of HFD with blueberry reduced these memory deficits. As a follow-up to that study, brain tissue from HFD-fed mice with and without blueberry supplementation was assessed to determine the neuroprotective mechanism(s) by which blueberry allayed cognitive dysfunction associated with HFD. Methods: Mice were fed HFDs (60% calories from fat) or low fat diets (LFD) with and without 4% blueberry (freeze-dried, U.S. Highbush Blueberry Council). Microglia activation was assessed ex vivo and in vitro. The hippocampus was assessed for brain-derived neurotrophic factor (BDNF) and neurogenesis by measuring doublecortin (DCX). Results: There was significantly less microglia Iba1 staining in mice fed HFD + blueberry compared to mice fed LFD and HFD. BV-2 microglial cells treated with serum collected from the mice fed the diets supplemented with blueberry produced less nitric oxide compared to cells treated with serum from mice fed HFD. BDNF levels were higher and the number of DCX positive cells was greater in the hippocampus of mice fed HFD + blueberry compared to mice fed HFD. Discussion: This study demonstrated that supplementation of a HFD with blueberry reduced indices of microglia activation and increased neuroplasticity, and these changes may underlie the protection against memory deficits in HFD-fed mice supplemented with blueberry.