SUPPLEMENTATION OF OMEGA-3 AND MEMBRANE LIPIDS DURING ADOLESCENCE IMPROVES COGNITIVE FUNCTION AND PREFRONTAL CORTEX INTEGRITY IN PRECLINICAL MODEL

Adolescence is a critical window of brain maturation, during which the brain is particularly sensitive to environment and diet. Lipids, including docosahexaenoic acid (DHA), choline, lutein, zeaxanthin, sphingomyelin support brain maturation acting on neuronal membranes and myelination. Here, we investigated whether a diet enriched with these and specific lipids, such as palmitoleic acid (POA), improved cognitive function in adolescent CD1 mice. Immediately after weaning, postnatal day (PND) 21, mice were provided a control diet (CD), a diet enriched with the aforementioned lipids (enriched diet with palmitoleic acid, herafter ED+POA), or a diet with the same enriched formulation, except POA (enriched diet, herafter ED). Between PND35 and PND60, we assessed the following cognitive domains: cognitive flexibility via the Attentional set-shifting task (ASST), spatial memory (Barnes maze), and anxiety-like behaviour (Elevated 0-maze). We then investigated structural and metabolic fluctuations in hippocampus and prefrontal cortex via magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI). Both enriched diets improved cognitive and behavioural flexibility in terms of fewer errors in extra-dimensional shift stage of the ASST and reduced latency during the acquisition of the Barnes maze reversal phase (p<0.05). In ED mice, behavioural improvements were associated with increased N-acetylaspartate levels and higher fractional anisotropy selectively in the prefrontal cortex, suggesting enhanced neuronal metabolism and microstructural organisation. These results highlight that the supplementation of selected lipids during adolescence may promote cognitive flexibility and prefrontal cortex integrity.
C.T., E.P., G.P., R.C., S.M. declare no conflict of interest. C-E.R., E.G., J.H, D.B are employees of Nestlé.