Maternal omega-3 deficiency can impair the development of neuronal networks in offspring



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Omega-3 fatty acids are essential, necessarily supplied by the diet and indispensable for brain development.

Scientists from INRAE ​​and the University of Bordeaux, working in collaboration with INSERM, Laval and Toronto universities in Canada and other partners (Harvard, Fondation Basque, etc.) have focused in particular on the impact of maternal diet during gestation and lactation on the developing brain of their offspring.

They thus demonstrated for the first time in mice how an insufficient supply of omega-3 in the mother can alter the development of neuronal networks in the offspring, causing memory deficits. They also deciphered the molecular mechanisms behind these effects. This unprecedented work, which is the result of several years of research, was published on November 30, 2020 in Nature Communications.

Essential fatty acids (omega 3 and 6) are massively incorporated into the brain of the offspring through the maternal diet during gestation and lactation. Fragmented scientific results have indicated that an insufficient consumption of these fatty acids by the mother during the perinatal period constitutes a risk factor for cognitive deficits in children (language, memory, learning, etc.).

But what is the causal mechanism? INRAE ​​scientists from the Nouvelle-Aquitaine Research Center and the University of Bordeaux, and their colleagues, focused on a particular type of cell in the brain: microglial cells (or microglia) that participate in the formation of neuronal networks that support memory skills. These brain macrophages are found at the interface between the environment and neurons.

During brain development, microglia “sculpt” neuronal networks by “swallowing” unnecessary synapses – the connectors between neurons – and retaining only those essential for satisfactory brain function.

The scientists focused their studies on a mouse model to determine whether maternal omega-3 status – and therefore that of offspring – could exert an effect on microglia activity.

Omega 3 deficiency affects the activity of a particular type of cell in the mouse brain
The results showed for the first time that an insufficient intake of omega 3 through the maternal diet affects the activity of microglia in the developing brain; these cells behave abnormally and become hyperphagic; that is, they lose the ability to recognize the synapses that had to be canceled, “incorporating” too many of them.

The neuronal network is therefore poorly formed, causing deficits in the memory skills of the offspring. Scientists were also able to decipher the molecular mechanisms responsible for this abnormal microglia activity.

To study this link between omega-3 intake and brain development, scientists also developed several innovative technologies to evaluate the modification of microglia behavior towards synapses, to analyze their lipid content, and to test different molecules in order to identify those responsible for this dysfunction and determine how it could be restored.

This work offers new perspectives for research and studies will continue in humans to better understand the links between omega 3 and brain development. In the general population, many pregnant women are omega 3 deficient, and early identification of those at risk could allow for preventive measures to offset this deficiency.

Omega 3 fatty acids are a family of essential fatty acids. This contains fatty acids which are essential for developing satisfactory body functioning, but can only be provided by the diet. They are found in numerous vegetable oils (nuts, canola, linseed, etc.) and in the meat of fatty fish.

Source:

Journal reference:

Madore, C., et al. (2020) Omega-3 essential fatty acids regulate microglial phagocytosis of synaptic elements in the developing mouse brain. Nature Communications. doi.org/10.1038/s41467-020-19861-z.

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