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

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- 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-, 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- 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- 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid- 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.