1. Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of β-Amyloid in a mouse model with Alzheimer’s disease
- Author
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Huanxing Su, Xiaoli Yao, Lingli Yan, Qiang Liu, Youna Xie, Yuemeng Ma, Senthil Kumaran Satyanarayanan, Jian-Bo Wan, Miaodan Huang, Haitao Zeng, and Kuan-Pin Su
- Subjects
0301 basic medicine ,Genetically modified mouse ,medicine.medical_specialty ,Immunology ,Mice, Transgenic ,Amyloid beta-Protein Precursor ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,medicine ,Extracellular ,Animals ,Senile plaques ,Neuroinflammation ,chemistry.chemical_classification ,Amyloid beta-Peptides ,Endocrine and Autonomic Systems ,Chemistry ,Brain ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Tumor necrosis factor alpha ,Alzheimer's disease ,030217 neurology & neurosurgery ,Lipoprotein ,Polyunsaturated fatty acid - Abstract
Amyloid-β (Aβ) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between Aβ production and clearance leads to extracellular Aβ accumulation in the brain. It is reported that the blood–brain barrier (BBB) transport plays a predominant role in Aβ clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted Aβ clearance from the bran to circulation, as revealed by reduced soluble/insoluble Aβ levels and senile plaques in the brain parenchyma and a corresponding increase of Aβ levels in plasma. Besides, fish oil supplement significantly inhibited the NF-κB activation, reduced the expression of interleukin-1β and tumor necrosis factor-α, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to Aβ pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting Aβ clearance from brain-to-blood.
- Published
- 2020