Metabolomics

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Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain


ABSTRACT:

Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, partly through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.

INSTRUMENT(S): Liquid Chromatography MS -

SUBMITTER: Agnes Nadjar  

PROVIDER: MTBLS1952 | MetaboLights | 2020-11-03

REPOSITORIES: MetaboLights

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Publications

Chronic dietary n-6 PUFA deprivation leads to conservation of arachidonic acid and more rapid loss of DHA in rat brain phospholipids.

Lin Lauren E LE   Chen Chuck T CT   Hildebrand Kayla D KD   Liu Zhen Z   Hopperton Kathryn E KE   Bazinet Richard P RP  

Journal of lipid research 20141204 2


To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of (3)H-ARA or (3)H-DHA. Brains were collected at fixed times over 128 days to determine half-lives and the rates of loss from brain phospholipids (J out). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rat  ...[more]

Publication: 1/2

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