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

Nutr Neurosci. 2019 Apr;22(4):253-263. doi: 10.1080/1028415X.2017.1376472. Epub 2017 Sep 21.


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, the 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 ionized calcium binding adaptor molecule 1 staining and fewer microglia in the brains of 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.

Keywords: BDNF; Berry; Blueberry; High-fat diet; Hippocampus; Microglia; Neurogenesis; Neuroplasticity.

MeSH terms

  • Animals
  • Blueberry Plants*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Diet, High-Fat / adverse effects*
  • Hippocampus / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • NADPH Oxidase 4 / metabolism
  • Neurogenesis
  • Neuronal Plasticity*
  • Nitric Oxide / metabolism


  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Nitric Oxide
  • NADPH Oxidase 4
  • Nox4 protein, mouse