2026 ECNP Congress

PS03-3016

Omega-3 and membrane lipids supplementation during adolescence improves cognitive function and preserves prefrontal cortex integrity in preclinical model

Cristiana Tonelli — E. Pisa, C.E. Rouault, E. Gebara, P. Gianmauro, R. Canese, J. Hauser, D. Brkić, S. Macrì · University of Parma, Medicine and Surgery, Parma, Italy

2026 ECNP Congress

Introduction

The majority of brain growth occurs during the first five years of life, reaching about 90% of adult brain size [1]. However, grey and white matter components continue to undergo dynamic changes throughout adolescence. Adolescence represents a critical developmental window characterised by intense brain maturation, synaptic pruning and myelination [2]. These developmental processes make individuals vulnerable to environmental and dietary factors, which can exert both beneficial and detrimental effects on brain structure and function [3,4]. Lipids such as docosahexaenoic acid (DHA), choline, lutein, zeaxanthin, and sphingomyelin play crucial roles in maintaining neuronal membrane integrity, synaptic function, neurotransmission and myelin formation [5]. This study aimed to investigate the effects of a nutrient-enriched diet during periadolescence on cognitive function in mice. In particular, it sought to demonstrate that a diet enriched with these specific lipids improves cognitive function in a mouse model during periadolescence, and to explore whether the addition of palmitoleic acid (POA), a monounsaturated fatty acid with neuroprotective properties, further enhances these beneficial effects.

Methods

The study was conducted on male and female CD1 mice. Immediately after weaning, postnatal day (PND) 21, mice were randomly assigned to one of three dietary conditions: (i) control diet (CD): standard laboratory chow diet with balanced macronutrient content; (ii) enriched diet (ED): diet supplemented with key nutrients supporting neurodevelopment and cognitive function, including DHA, lutein, zeaxanthin, iron, folate, choline, vitamin B12 and B9, sphingomyelin; (iii) enriched diet + palmitoleic acid (ED+POA): same formulation as the ED, further supplemented with POA. Between PND35 and PND60, cognitive domains were evaluated through Attentional set-shifting task (cognitive flexibility), Barnes maze (spatial memory and reversal learning), and Elevated zero-maze (anxiety-like behaviour). In parallel, neuroimaging techniques, such as magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI), were used to correlate behavioural outcomes with structural and metabolic changes in the brain. Data were analysed through repeated analysis of variance (ANOVA) for split-plot designs. Post-hoc comparisons were performed using Tukey’s significant difference test.

Results

Both enriched diets improved cognitive and behavioural flexibility in terms of fewer errors in the extra-dimensional shift stage of the attentional set-shifting task and reduced latency during the acquisition of the Barnes maze reversal phase compared to control (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.

Conclusions

Supplementation with selected lipids during adolescence appears to improve cognitive flexibility and learning performancein mice. These effects are associated with changes in pre-frontal cortex myelination, suggesting more efficient neuronal function. Dietary lipids may represent a promising strategy to support brain development during adolescence.

The study has been funded by Nestlè. C. Tonelli, E. Pisa, G. Palombelli, R. Canese, S. Macrì have no conflict of interest. C.E. Rouault, E. Gebara, J. Hauser, D. Brkić are employees of Nestlé.

References

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  2. Norris SA, Frongillo EA, Black MM, et al. Nutrition in adolescent growth and development. Lancet. 2022;399(10320):172-184. doi:10.1016/S0140-6736(21)01590-7
  3. Soliman A, De Sanctis V, Elalaily R. Nutrition and pubertal development. Indian J Endocrinol Metab. 2014;18(Suppl 1):S39-S47. doi:10.4103/2230-8210.145073
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