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Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of β-Amyloid in a mouse model with Alzheimer’s disease
- Source :
- Brain, Behavior, and Immunity. 85:35-45
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.
- 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
Subjects
Details
- ISSN :
- 08891591
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Brain, Behavior, and Immunity
- Accession number :
- edsair.doi.dedup.....3265365bb50535f6b342a020848a61f4