Dietary fish oil, and to a lesser extent the fat-1 transgene, increases astrocyte activation in response to intracerebroventricular amyloid-β 1–40 in mice

Abstract

Objectives: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer’s disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear.

Methods: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques.

Results: GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals.

Conclusion: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.

Keywords:

• Alzheimer’s disease
• Astrocyte
• n-3 Polyunsaturated fatty acids
• Docosahexaenoic acid
• Amyloid-β
• Neuroinflammation
• Fish

Disclaimer statements

Contributors KEH wrote the paper and conducted all the work to acquire the brain images, which were then analysed by DM, NCEJ, and MI. RPB oversaw the project. All authors reviewed and provided feedback on the manuscript.

Funding This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to RPB, a CIHR Vanier Canada Graduate Scholarship to KEH and a National Sciences and Engineering Research Council of Canada Undergraduate Student Research Award to DM and NCEJ.

Conflict of interest RPB has received research grants from Bunge Ltd, Arctic Nutrition, the Dairy Farmers of Canada and Nestle Inc, as well as travel support from Mead Johnson and mass spectrometry equipment and support from Sciex. RPB is on the executive of the International Society for the Study of Fatty acids and Lipids and held a meeting on behalf of Fatty Acids and Cell Signalling, both of which rely on corporate sponsorship. RPB has given expert testimony in relation to supplements and the brain. RPB also provides complimentary fatty acid analysis for farmers, food producers and others involved in the food industry, some of whom provide free food samples.

Ethics approval None.

Supplemental data Supplemental materials for this article can be accessed at doi:10.1080/1028415X.2017.1396068.