Omega-3 polyunsaturated fatty acids in the brain: metabolism and neuroprotection

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a group of essential fatty acids that serve as energy substrates and integral membrane components, and therefore play crucial roles in the maintenance of normal neurological function. Recent studies show that n-3 PUFAs display neuroprotective properties and exert beneficial effects on the cognitive function with aging. The brain's need of n-3 PUFAs is predominantly met by the blood delivery due to their limited synthesis in the brain. The present review focuses on the metabolism of n-3 PUFAs in the brain, including their accumulation and turnover. We also highlight the current understanding of the neuroprotective effects of n-3 PUFAs against cerebral ischemia and neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

Neurite outgrowth stimulation by n-3 and n-6 PUFAs of phospholipids in apoE-containing lipoproteins secreted from glial cells

“…Astrocytes and endothelial cells, major cellular components of the blood-brain barrier, may play important roles in the delivery of PUFAs to neurons ( 40,43 ). Recently, Nguyen et al ( 44 ) reported that Mfsd2a, a transmembrane protein specifi c to the endothelium of the blood-brain barrier, transfers DHA in the form of lysoPC into endothelial cells.…”

“…n-3 and n-6 PUFAs stimulate neurite outgrowth by acting on syntaxin 3, which is mainly localized in neuronal growth cones, in order to allow membrane expansion ( 41,42 ). As components of cell membranes, PUFAs in phospholipids increase membrane fl uidity, altering the function of membrane proteins and vesicle budding and fusion, which are important for neurite outgrowth ( 43 ). It is likely that PUFAs exert their effects through multiple mechanisms.…”

Enriched endogenous omega-3 fatty acids in mice protect against global ischemia injury

“…Exogenous application of -3 PUFAs slowed the progression of Alzheimer's disease in mice ( 33,34 ), prevented Huntington's disease ( 35 ), showed therapeutic potential for spinal cord injury (36)(37)(38)(39), and improved neurological and histological outcomes in the focal cerebral ischemia model ( 5,(40)(41)(42). However, these beneficial effects of -3 PUFAs are not consistently detected ( 13,43 ). One of the reasons is that feeding animals with different experimental diets may impose confounding Fig.…”

“…For example, fat-1 mice exhibited increased hippocampal neurogenesis evidenced by elevated density of dendritic spines of CA1 neurons, leading to a better spatial learning performance in the Morris Water Maze compared with control the last several decades, the ratio of -6/ -3 PUFAs in the diet has changed dramatically from 1-2:1 previously to 15-20:1 presently, which leads to an increase in the intake of -6 PUFAs and a concomitant decrease in the intake of -3 PUFAs ( 30 ). The defi ciency in -3 PUFAs is considered to be a risk factor for human mental and neurological disorders ( 13,31,32 ). Exogenous application of -3 PUFAs slowed the progression of Alzheimer's disease in mice ( 33,34 ), prevented Huntington's disease ( 35 ), showed therapeutic potential for spinal cord injury (36)(37)(38)(39), and improved neurological and histological outcomes in the focal cerebral ischemia model ( 5,(40)(41)(42).…”

Fatty acids rehabilitated long-term neurodegenerative: like symptoms in olfactory bulbectomized rats

“…The relationships between AD, dementia, and fatty acids seem to be very complex. Many studies have found a correlation between lower PUFA levels and the risk of AD (for example, Cole et al 2009;Cunnane et al 2012;Kyle et al 1999;Swanson et al 2012;Zhang et al 2011). On the other hand, some studies have reported conflicting results regarding the beneficial effects of PUFA supplementation in AD (for example, Dangour et al 2012;Mazereeuw et al 2012;Ronnemaa et al 2012;Tan et al 2012).…”