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An omega 3 deficiency may explain some depressive behaviours

The effects of a maternal diet deficient in essential fatty acids on the brain of her infant are poorly understood. However, it is known that a lack of omega 3 fatty acids is implicated in numerous pathologies. INSERM and INRA researchers, working in association with Spanish scientists, monitored mice receiving an omega 3-depleted diet and discovered that low omega 3 levels impaired the functions of neurons involved in the control of emotional behaviours.

Pavés de saumon.. © INRA, CAIN Anne-Hélène
Updated on 05/31/2013
Published on 07/20/2011

Levels of essential fatty acids in the diet of populations in industrialised countries have fallen since the start of the 20th century. Thus the ratio between amounts of omega 6 and omega 3 polyunsaturated fatty acids has risen steadily throughout the past century. These fatty acids are "essential" lipids because the body itself cannot synthesise them, so they must be supplied via the diet. Lipids are essential to the functioning of the nervous system and their equilibrium needs to be preserved in the brain.

Olivier Manzoni, a Senior Researcher at INSERM (Unit 862 "Neurocentre Magendie" in Bordeaux and Unit 901 "Institut de Neurobiologie de la Méditerranée Marseille") and Sophie Layé, Senior Scientist at Inra (Unit 1286 "Nutrition and Integrative Neurobiology" in Bordeaux) and their colleagues have advanced the hypothesis that chronic malnutrition, starting as early as the intra-uterine development stage, can influence the activity of neurons involved in emotional behaviours (depression, anxiety, etc.) during adulthood.

To verify their hypothesis, the scientists monitored mice subjected to a diet that reflected this imbalance between omega 3 and omega 6 fatty acids. They discovered that an omega 3 deficiency in the brain disturbed nerve impulse transmissions…. but not just of any type! Indeed, the scientists observed that only cannabinoid receptors, which are of strategic importance to nerve impulse transmission, saw an abolition of their function. This neuronal dysfunction was accompanied by depressive behaviour in these malnourished mice.

Endocannabinoids (endoCB) exert a long-term effect on synaptic plasticity thanks to their retrograde action on the presynaptic element.

The endogenous cannabinoid (endocannabinoid) system is very widely expressed in the central nervous system where it participates in synaptic transmissions. From the physiological and behavioural points of view, the endocannabinoid system is fundamental to pain, learning, food intake and emotional behaviours.

There are two principal endocannabinoids, which are signal lipids made up of long chains of fatty acids. They are produced in response to neuronal activity and activate specific receptors called cannabinoid receptors. The main cannabinoid receptors expressed in the central nervous system are called CB1R.

The endocannabinoid system is a major actor in synaptic plasticity and its deregulation is known to be implicated in mood disorders.

In omega 3-deficient mice, the usual effects generated by the activation of cannabinoid receptors, at both the synaptic and behavioural levels, were no longer seen. Thus the CB1R receptors lost their activity at the synaptic level, and the anxiogenic effect of cannabis disappeared.

As a result, the researchers discovered that in mice subjected to an omega 3-deficient diet, the synaptic plasticity dependent upon CB1R cannabinoid receptors was disturbed in at least two structures implicated in reward, motivation and emotional regulation: the prefrontal cortex and the nucleus accumbens. Indeed, these parts of the brain contain a large number of CB1R cannabinoid receptors, and there are important functional connections between them.

"Our findings now corroborate those of clinical and epidemiological studies that demonstrated links between an omega 3/omega 6 imbalance and mood disorders", explain Olivier Manzoni and Sophie Layé. "Of course, it is now necessary to carry out further studies to determine whether omega 3 deficiencies are responsible for these neuropsychiatric disorders".

In conclusion, the authors consider that their findings provide the first biological evidence to explain the correlations observed between omega 3-deficient diets, which are very widespread in the industrialised world, and mood disorders such as depression.

Scientific contact(s):

  • Sophie Layé (05 57 57 12 32) Inra, NutriNeuro Nutrition et Neurobiologie intégrée, 146 rue Léo Saignat, 3077 BORDEAUX, France
  • Olivier Manzoni (04 91 82 81 37) Inserm, Physiopathology of Synaptic Plasticity Group, Neurocentre Magendie, 146 Rue Léo—Saignat, 33077 Bordeaux
Associated Centre(s):