Maternal n-3 polyunsaturated fatty acid dietary supply modulates microglia lipid content in the offspring

Rey, Charlotte; Nadjar, Agnès; Joffre, Florent; Amadieu, Camille; Aubert, Agnès; Vaysse, Carole; Pallet, Véronique; Layé, Sophie; Joffre, Corinne

doi:10.1016/j.plefa.2018.04.003

Cited by 40 publications

(29 citation statements)

References 87 publications

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“…This is further supported by the negative correlation between hippocampal learning and CD68 expression. Additionally, microglia might also contribute to the changes in neurogenesis because, among their many functions, microglia play critical roles in synaptic tuning and pruning of newborn neurons (79–81), thereby contributing to the beneficial effects on cognition after ES. Contributing to the cognitive impairments as well as the alterations in the neuroinflammation that we observe after ES and diet, inflammatory changes and oxidative mechanisms in the circulatory and gastrointestinal systems may be involved as well (82).…”

Section: Discussionmentioning

confidence: 99%

Increasing availability of ω‐3 fatty acid in the early‐life diet prevents the early‐life stress‐induced cognitive impairments without affecting metabolic alterations

et al. 2019

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Exposure to early‐life stress (ES) is associated with cognitive and metabolic deficits in adulthood. The role of early nutrition in programming these long‐term effects is largely unknown. We focused on essential ω‐3 and ω‐6 long‐chain polyunsaturated fatty acids (LCPUFA) and investigated whether ES affects central and peripheral FA profiles, as well as if and how an early diet with increased availability of ω‐3 LCPUFA (via lowering ω‐6/ω‐3 ratio) protects against ES‐induced impairments. ES exposure [limited nesting and bedding paradigm from postnatal day (P)2 to P9] altered central and peripheral FA profiles in mice. An early diet with low ω‐6/ω‐3 ratio from P2 to P42 notably prevented the ES‐induced cognitive impairments, and the alterations in hippocampal newborn cell survival and in CD68+ microglia, without affecting the ES‐induced metabolic alterations. Other markers for hippocampal plasticity, apoptosis, and maternal care were unaffected by ES or diet. Our findings highlight the importance of early dietary lipid quality for later cognition in ES‐exposed populations.—Yam, K.‐Y., Schipper, L., Reemst, K., Ruigrok, S. R., Abbink, M. R., Hoeijmakers, L., Naninck, E. F. G., Zarekiani, P., Oosting, A., Van der Beek, E. M., Lucassen, P. J., Korosi, A. Increasing availability of ω‐3 fatty acid in the early‐life diet prevents the early‐life stress‐induced cognitive impairments without affecting metabolic alterations. FASEB J. 33, 5729–5740 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Increasing availability of ω‐3 fatty acid in the early‐life diet prevents the early‐life stress‐induced cognitive impairments without affecting metabolic alterations

et al. 2019

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“…We provide novel knowledge on highly targetable cellular and molecular pathways linking maternal nutrition and neurodevelopmental disorders. Indeed, specific dietary strategies can enhance PUFA status in microglia 106 , being promising avenues for the prevention and treatment of neurodevelopmental disorders.…”

Section: Discussionmentioning

confidence: 99%

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

Madore

Leyrolle²,

Morel

et al. 2019

Preprint

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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-3PUFAs. 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, 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.One Sentence Summary: Low maternal omega-3 fatty acids intake impairs microgliamediated synaptic refinement via 12-HETE pathway in the developing brain.

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“…This is further supported by the negative correlation between hippocampal learning and CD68 expression. Additionally, microglia might also contribute to the changes in neurogenesis because, among their many functions, microglia play critical roles in synaptic tuning and pruning of newborn neurons (79)(80)(81), thereby contributing to the beneficial effects on cognition after ES. Contributing to the cognitive impairments as well as the alterations in the neuroinflammation that we observe after ES and diet, inflammatory changes and oxidative mechanisms in the circulatory and gastrointestinal systems may be involved as well (82).…”

Section: Potential Mechanisms Underlying the Beneficial Effects Of Thmentioning

confidence: 99%

Hospital transfer after a breast cancer diagnosis: A population-based study in the Netherlands of the extent, predictive characteristics and its impact on time to treatment

Heeg

Schreuder²,

Spronk

et al. 2019

European Journal of Surgical Oncology

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Exposure to early-life stress (ES) is associated with cognitive and metabolic deficits in adulthood. The role of early nutrition in programming these long-term effects is largely unknown. We focused on essential v-3 and v-6 long-chain polyunsaturated fatty acids (LCPUFA) and investigated whether ES affects central and peripheral FA profiles, as well as if and how an early diet with increased availability of v-3 LCPUFA (via lowering v-6/v-3 ratio) protects against ES-induced impairments. ES exposure [limited nesting and bedding paradigm from postnatal day (P)2 to P9] altered central and peripheral FA profiles in mice. An early diet with low v-6/v-3 ratio from P2 to P42 notably prevented the ES-induced cognitive impairments, and the alterations in hippocampal newborn cell survival and in CD68 + microglia, without affecting the ES-induced metabolic alterations. Other markers for hippocampal plasticity, apoptosis, and maternal care were unaffected by ES or diet. Our findings highlight the importance of early dietary lipid quality for later cognition in ES-exposed populations. Increasing availability of v-3 fatty acid in the early-life diet prevents the early-life stress-induced cognitive impairments without affecting metabolic alterations. FASEB J. 33, 5729-5740 (2019). www.fasebj.org

show abstract

Maternal n-3 polyunsaturated fatty acid dietary supply modulates microglia lipid content in the offspring

Cited by 40 publications

References 87 publications

Increasing availability of ω‐3 fatty acid in the early‐life diet prevents the early‐life stress‐induced cognitive impairments without affecting metabolic alterations

Increasing availability of ω‐3 fatty acid in the early‐life diet prevents the early‐life stress‐induced cognitive impairments without affecting metabolic alterations

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

Hospital transfer after a breast cancer diagnosis: A population-based study in the Netherlands of the extent, predictive characteristics and its impact on time to treatment

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