Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain.
Animals
Brain
/ drug effects
Dietary Supplements
Fatty Acids, Omega-3
/ deficiency
Female
Gene Expression Regulation, Developmental
/ drug effects
Hippocampus
/ cytology
Homeostasis
Humans
Lipoxygenase
Male
Mice
Microglia
/ drug effects
Neurodevelopmental Disorders
Neuronal Plasticity
/ drug effects
Neurons
/ drug effects
Phagocytosis
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 11 2020
30 11 2020
Historique:
received:
24
07
2019
accepted:
03
11
2020
entrez:
1
12
2020
pubmed:
2
12
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Omega-3 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 Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.
Identifiants
pubmed: 33257673
doi: 10.1038/s41467-020-19861-z
pii: 10.1038/s41467-020-19861-z
pmc: PMC7704669
doi:
Substances chimiques
Fatty Acids, Omega-3
0
Lipoxygenase
EC 1.13.11.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6133Subventions
Organisme : NINDS NIH HHS
ID : R01 NS088137
Pays : United States
Organisme : CIHR
Pays : Canada
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