Mechanism underlying effects of fish oil supplementation in presymptomatic stage of Alzheimer disease in 5XFAD mice

Abstract

Aims: Alzheimer’s disease (AD) is the most prevalent type of dementia in elderly,triggered by multiple factors such as amyloid plaques, neurofibrillary tangles and neuroinflammation. The use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology. The purpose of this study was to elucidate the mechanisms underlying effects of short-term fish oil (FO) suplementation in presymptomatic stage of AD in 5xFAD mice. Methods: Three-month old female 5xFAD mice received FO (100μl/animal/day) via oral gavage during the period of 3 weeks. Western blot and immunohistochemical analysis were used to detect changes in pathological features of AD in cortex of 5xFAD mice. AmiloGlo was used to visualize plaques. Amyloid beta (Aβ) peptide, dystrophic neurites (DNs), microglia/macrophages and CX3CR1/CX3CL1 were detect by anti-Aβ42-, anti-SMI31-, p-Tau-, anti-Iba-1-, anti-CX3CR1 anti-CX3CL1 antibodies, retrospectively. Immunostaining was observed by confocal microscopy. Quantification was done by Image J and Image Quant softwer. Results: The present study shows that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment suppresses CX3CR1/CX3CL1 axis, interaction between microglial cells and neurons, which represents one of possible mechanisms for altered microglial/macrophage motility and colocalization around plaques. Conclusion: Our findings suggest that FO consumption may play an important role in modulating microglial response and ameliorating the AD pathology in presymptomatic stage of Alzheimer’s disease.