N-3 PUFA deficiency affects the ultrastructural organization and density of white matter microglia in the developing brain of male mice

Date

2022

Authors

Decoeur, Fanny
Picard, Katherine
St-Pierre, Marie-Kim
Greenhalgh, Andrew D.
Delpech, Jean-Christophe
Sere, Alexandra
Layé, Sophie
Tremblay, Marie-Eve
Nadjar, Agnès

Journal Title

Journal ISSN

Volume Title

Publisher

Frontiers in Cellular Neuroscience

Abstract

Over the last century, westernization of dietary habits has led to a dramatic reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). In particular, low maternal intake of n-3 PUFAs throughout gestation and lactation causes defects in brain myelination. Microglia are recognized for their critical contribution to neurodevelopmental processes, such as myelination. These cells invade the white matter in the first weeks of the post-natal period, where they participate in oligodendrocyte maturation and myelin production. Therefore, we investigated whether an alteration of white matter microglia accompanies the myelination deficits observed in the brain of n-3 PUFA-deficient animals. Macroscopic imaging analysis shows that maternal n-3 PUFA deficiency decreases the density of white matter microglia around post-natal day 10. Microscopic electron microscopy analyses also revealed alterations of microglial ultrastructure, a decrease in the number of contacts between microglia and myelin sheet, and a decreased amount of myelin debris in their cell body. White matter microglia further displayed increased mitochondrial abundance and network area under perinatal n-3 PUFA deficiency. Overall, our data suggest that maternal n-3 PUFA deficiency alters the structure and function of microglial cells located in the white matter of pups early in life, and this could be the key to understand myelination deficits during neurodevelopment.

Description

We would like to thank Patrick Nahirney and Brent Gowen for the access to the transmission electron microscope. We would also like to thank Christel Poujol, Sébastien Marais, Fabrice Cordelières, Jérémie Teillon,Magali Mondin, Monica Fernandez-Monreal from the Bordeaux Imaging Center (Bordeaux, France) for their help with microscopy experiments and image analysis. We like to thank Maude Bordeleau for her help with image analyses. We finally thank the animal facility of the NutriNeuro lab for taking care of and providing the animals that were necessary to perform the experiments. We acknowledge and respect the Lək̓ʷəŋən people on whose traditional territory the University of Victoria stands and the Songhees, Esquimalt and W̱SÁNEĆ peoples whose historical relationships with the land continue to this day.

Keywords

n-3 PUFA, microglia, myelin, neurodevelopment, electron microscopy

Citation

Decoeur, F., Picard, K., St-Pierre, M-K., Greenhalgh, A. D., Delpech, J-C., Sere, A., ... Nadjar, A. (2022). N-3 PUFA deficiency affects the ultrastructural organization and density of white matter microglia in the developing brain of male mice. Frontiers in Cellular Neuroscience, 16, 802411. https://doi.org/10.3389/fncel.2022.802411