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EBioMedicine. 2018 Jun;32:50-61. doi: 10.1016/j.ebiom.2018.05.028. Epub 2018 Jun 5.

Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction.

Author information

1
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; Department of Neurology, Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 510080, China.
2
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
3
Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China.
4
Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
5
Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, College of Medicine, China Medical University, Taichung, Taiwan.
6
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: huanxingsu@umac.mo.

Abstract

Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these microvascular ischemic lesions. In the present study, the "single cortical microinfarct model" generated via occluding a penetrating arteriole by femtosecond laser ablation and the "multiple diffuse microinfarcts model" induced by unilateral injection of cholesterol crystals through the internal carotid artery were established to investigate the pathophysiological mechanisms underlying the evolution of microinfarcts and the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on alleviating microinfarct burdens and functional deficits. The occlusion of a single penetrating arteriole led to a distinct cortical microinfarct, which manifested as neuronal loss and occupation of activated glial cells in the ischemic core. Using Fat-1 transgenic mice and fish oil supplements, we demonstrated that both endogenously-generated and exogenously-delivered ω-3 PUFAs significantly inhibited the activation of receptor-interacting serine/threonine protein kinases 1 (RIPK1) and its downstream apoptosis-associated proteins, mitigated cell apoptosis, and anatomically reduced the microinfarct size. The protective effects of ω-3 PUFAs against microinfarcts were further verified in a multiple diffuse microinfarcts model, where ω-3 PUFAs significantly attenuated cell apoptosis as revealed by TUNEL staining, alleviated the diffuse microinfarct burdens and remarkably improved the functional deficits as evidenced by reduced spontaneous anxiety, increased preference for the novel object, and improved hippocampal-based learning and short-term memory. Together, these findings demonstrate that enriched brain ω-3 PUFAs are effective for reducing microinfarct burdens and improving the function deficits, which support the clinical research and application of ω-3 PUFAs in the treatment or prophylaxis in vascular dementia.

KEYWORDS:

Cognitive decline; Fish oil; Neuropsychiatric disorders; Vascular dementia

PMID:
29880270
PMCID:
PMC6021265
DOI:
10.1016/j.ebiom.2018.05.028
[Indexed for MEDLINE]
Free PMC Article

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