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Image of a mouse hippocampus with an omega-3 deficiency. Yellow: astrocytes; blue: neurons; red: microglial cells. © INRA, NutriNeuro

Why does the brain need omega-3?

Omega-3 and omega-6: what effect do polyunsaturated fatty acids (PUFA) have on the brain? Sophie Layé, director of INRA’s Joint Research Unit for Nutrition and Integrative Neurobiology (NutriNeuro; INRA–University of Bordeaux), and Richard Bazinet, professor at the University of Toronto, reviewed scientific and medical literature to understand the role of PUFAs in normal and pathological brains. Their report, published in Nature Reviews Neuroscience on 12 November 2014, also investigates new ways of understanding the protective effects fatty acids have against neuropsychiatric disorders and neurodegenerative diseases.

Updated on 07/04/2017
Published on 11/12/2014

Tuna, sardines, mackerel, and all other fatty fish are, in general, our main source of omega-3 polyunsaturated fatty acids (PUFA), although they can also be found in oils such as walnut and soybean oil. The major forms of PUFA found in the brain are docosahexaenoic acid (DHA) from the omega-3 family, and arachidonic acid (AA) from the omega-6 family. These lipids are created from precursors provided solely through dietary nutrients in the blood delivered to the brain. While the brain makes little use of DHA and AA as energy sources, these fatty acids and their derivatives are involved in a number of other processes such as neurotransmission, cell survival, and neuroinflammation, and thereby also play a role in mood and cognition.

Essential nutrients during perinatal period

In laboratory test animals, an omega-3 deficiency during embryonic development and the lactation phase alters the cerebral immune system and brain plasticity. This new finding was published in a recent study by researchers from the Nutrition and Integrative Neurobiology (NutriNeuro) joint research unit (INRA–University of Bordeaux)1. As development progresses, PUFAs are particularly important because they are major components of brain cell membranes. To avoid deficiencies, PUFA-intake must be ongoing; nutrient intake must be at appropriate levels over the developmental period and in adulthood.

The role of omega-3 in neuroinflammation, neurogenesis, and neuroprotection

Layé and Bazinet’s article reviewed current literature to understand the role of PUFAs in physiological cellular functions in the brain. The literature – including previous works by Layé and Bazinet themselves – demonstrated that DHA and AA regulate synaptic activity through the actions of endocannabinoids and through endocannabinoid synthesis. Endocannabinoids are fat derivatives that control excitatory and inhibitory synapses by liberating vesicular neurotransmitters)2. The authors highlight the role of DHA and AA in neurogenesis and neuroprotection. They contribute to supplying the brain with glucose – the brain’s main source of energy – and are powerful neuroinflammation modulators. While the nature and activity of AA metabolites (prostaglandins, leukotrienes, etc.) in inflammatory situations are well understood, that is not the case for DHA derivatives (neuroprotectin, resolvin, etc.), which require further study, particularly in terms of their role in the resolution of neuroinflammation.

Boost memory with omega-3

In 2012, researchers from INRA and the University of Bordeaux demonstrated that a diet rich in DHA reduces neuroinflammation and the onset of cognitive impairment (such as memory loss) in aged mice3. More recently, researchers from the NutriNeuro joint research unit confirmed these findings using a transgenic mouse strain that displayed endogenously elevated omega-3 PUFAs in the brain. By inducing an inflammatory episode, they showed that the cognitive performance of the transgenic mice was normal and their neural plasticity preserved, while the opposite was true of the mice in the control group4.

Protection from depression

What is the role and the involvement of PUFAs in neuropsychiatric and neurodegenerative diseases? A considerable body of research has linked reduced levels of omega-3 PUFAs in the blood and brain to depression, schizophrenia, and Alzheimer’s disease in humans. Recent work carried out by researchers at the NutriNeuro joint research unit looked at how emotional behaviour in mice is disrupted by an unbalanced diet. The researchers established that omega 3 PUFA deficiency modulates morphology in the prefrontal cortex, leading to chronic stress and the development of anxiety behaviours. Their findings also demonstrated the role of an omega-3-rich diet in preventing occurrences of depression5. These findings are consistent with clinical trials carried out with omega-3 dietary supplements that showed improved effectiveness of certain drug treatments, thereby unlocking new possibilities for treatment strategies. This research also seeks to identify the level of omega-3 PUFA intake best suited for optimum brain function and protection, particularly when dealing with neuropathological incidents.

Image of a mouse hippocampus with an omega-3 deficiency. Yellow: astrocytes; blue: neurons; red: microglial cells.. © INRA, NutriNeuro
Image of a mouse hippocampus with an omega-3 deficiency. Yellow: astrocytes; blue: neurons; red: microglial cells. © INRA, NutriNeuro

Creation of INRA’s first associated international laboratory: LIA OptiNutriBrain

On 3 November 2014, François Houllier, INRA’s president, and representatives from the University of Bordeaux and the University of Laval, signed an agreement creating an associated international laboratory (LIA) on brain nutrition and health. Sophie Layé (INRA, Bordeaux) and Frédéric Calon (University of Laval, Québec) will jointly manage the France–Canada LIA, which aims to become a world leader in brain nutrition and health. It will carry out research to establish an optimum nutrition for maintaining brain function throughout life.

1Madore, C., et al. (2014) Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes. Brain Behavior, and Immunity 41:22-31
2Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matias I, De Smedt-Peyrusse V, Labrousse VF, Bretillon L, Matute C, Rodríguez-Puertas R, Layé S*, Manzoni OJ* (equal contribution) (2011) Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nature Neuroscience.14(3):345-50.
3Labrousse VF, Nadjar A, Joffre C, Costes L, Aubert A, et al. (2012) Short-Term Long Chain Omega 3 Diet Protects from Neuroinflammatory Processes and Memory Impairment in Aged Mice. PLoS ONE 7(5) e36861. doi:10.1371
4Delpech JC, Madore C, Joffre C, Aubert A, Kang JX, Nadjar A and Layé,S (2014) Transgenic Increase in n-3/n-6 Fatty Acid Ratio Protects Against Cognitive Deficits Induced by an Immune Challenge through Decrease of Neuroinflammation. Neuropsychopharmacology advance online publication, 17 September 2014; doi:10.1038/npp.2014.196
5T Larrieu, LM Hilal, C Fourrier, V De Smedt-Peyrusse, Sans N, L Capuron and S Layé (2014) Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behavior through corticosterone secretion. Translational Psychiatry 4, e437

Scientific contact(s):

  • Sophie Layé (+33 (0)5 57 57 92 18) Joint Research Unit for Nutrition and Integrated Neurobiology (INRA, University of Bordeaux)
Press Relations:
INRA News Office (+33 (0)1 42 75 91 86)
Associated Division(s):
Nutrition, Chemical Food Safety and Consumer Behaviour
Associated Centre(s):


Polyunsaturated fatty acids and their metabolites in brain function and disease, Richard P. Bazinet and Sophie Layé. Nature Reviews Neuroscience, published online on 12 November 2014. DOI: 10.1038/nrn3820