Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.

N-3 and n-6 polyunsaturated fatty acids (PUFAs) are essential fatty acids that are provided by dietary intake. Growing evidence suggests that n-3 and n-6 PUFAs are paramount for brain functions. They constitute crucial elements of cellular membranes, especially in the brain. They are the precursors of several metabolites with different effects on inflammation and neuron outgrowth. Overall, long-chain PUFAs accumulate in the offspring brain during the embryonic and post-natal periods. In this review, we discuss how they accumulate in the developing brain, considering the maternal dietary supply, the polymorphisms of genes involved in their metabolism, and the differences linked to gender. We also report the mechanisms linking their bioavailability in the developing brain, their transfer from the mother to the embryo through the placenta, and their role in brain development. In addition, data on the potential role of altered bioavailability of long-chain n-3 PUFAs in the etiologies of neurodevelopmental diseases, such as autism, attention deficit and hyperactivity disorder, and schizophrenia, are reviewed.

Long-chain (LC) n-3 polyunsaturated fatty acids (PUFAs) have drawn attention in the field of neuropsychiatric disorders, in particular depression. However, whether dietary supplementation with LC n-3 PUFA protects from the development of mood disorders is still a matter of debate. In the present study, we studied the effect of a two-month exposure to isocaloric diets containing n-3 PUFAs in the form of relatively short-chain (SC) (6% of rapeseed oil, enriched in α-linolenic acid (ALA)) or LC (6% of tuna oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) PUFAs on behavior and synaptic plasticity of mice submitted or not to a chronic social defeat stress (CSDS), previously reported to alter emotional and social behavior, as well as synaptic plasticity in the nucleus accumbens (NAc). First, fatty acid content and lipid metabolism gene expression were measured in the NAc of mice fed a SC (control) or LC n-3 (supplemented) PUFA diet. Our results indicate that LC n-3 supplementation significantly increased some n-3 PUFAs, while decreasing some n-6 PUFAs. Then, in another cohort, control and n-3 PUFA-supplemented mice were subjected to CSDS, and social and emotional behaviors were assessed, together with long-term depression plasticity in accumbal medium spiny neurons. Overall, mice fed with n-3 PUFA supplementation displayed an emotional behavior profile and electrophysiological properties of medium spiny neurons which was distinct from the ones displayed by mice fed with the control diet, and this, independently of CSDS. Using the social interaction index to discriminate resilient and susceptible mice in the CSDS groups, n-3 supplementation promoted resiliency. Altogether, our results pinpoint that exposure to a diet rich in LC n-3 PUFA, as compared to a diet rich in SC n-3 PUFA, influences the NAc fatty acid profile. In addition, electrophysiological properties and emotional behavior were altered in LC n-3 PUFA mice, independently of CSDS. Our results bring new insights about the effect of LC n-3 PUFA on emotional behavior and synaptic plasticity.

Taste perception is essential for animals to detect nutrients, providing critical dietary information necessary for growth and survival. Since the early growth performance of alevin rainbow trout ( Oncorhynchus mykiss ) can be affected by food intake influenced by terrestrial ingredients without fish meal and fish oil, our study aimed to evaluate the role of taste receptors in nutrient detection and the associated signaling pathways leading to central nervous system activation in the regulation of feeding behavior. We conducted a nutritional experiment from the first feeding to 30 days, comparing the performance of fish fed a commercial‐like diet (C diet: a blend of fish meal, fish oil, and plant ingredients) with those on a totally plant‐based diet (V diet). After 5 and 30 days of feeding, fish were fasted for 16 h and then fed either the C or V diet, with sampling conducted at 20 min and 6 h post‐meal. We evaluated the expression of nutrient‐sensing genes related to fatty acids, amino acids, and sweetness, and taste receptor genes for flavors. Additionally, we examined calcium signaling pathways in the tongue, focusing on indolamine and catecholamine pathways, alongside appetite‐regulating neuropeptides in the brain and intestinal hormones in the gut of alevins. Results indicated that fish on the V diet experienced a decrease in body weight gain starting 10 days after feeding to 30 days, along with changes in feed intake during the periods of 0–10 days and 21–30 days after the first meal. In tongue tissue, after 5 days of feeding, fish on the C diet showed a slight upregulation of nutrient taste receptors, but not those related to flavor, along with an upregulation of the calcium signaling pathway. By 30 days, there was a general upregulation of nutrient and flavor taste receptors, although the calcium signaling pathway showed less clear evidence of regulation. A significant dysregulation of the serotonin pathway, along with its degradation, was observed in the tongues of fish fed the V diet at both 5 and 30 days. For the first time in fish, catecholamine quantification levels in the tongue emerged as a potential marker for nutrient detection, with high quantification of L‐DOPA after 5 days on the V diet, but much lower after 30 days. This impaired monoamine and catecholamine turnover in the tongue could be linked to a failure in activating the tongue‐brain axis, potentially contributing to reduced food intake, as indicated by poorly regulated brain neuropeptides but also intestinal hormones in fish fed the V diet after 30 days. Overall, these findings demonstrate that the V diet disrupts the feeding response at an early stage, underscoring the heightened sensitivity of rainbow trout alevins’ tongue sensing systems to novel food sources during critical early development.

Le cerveau est riche en acides gras polyinsaturés (AGPI) dont les chaînes longues, comme l’acide docosahexaénoïque (DHA) et l’acide ecosapentaénoïque (EPA) issus des oméga 3 (n-3), s’accumulent au cours du développement. Leurs précurseurs ne sont pas synthétisés de novo par les mammifères et doivent être apporté par la nourriture. Or, il a été démontré qu’un apport nutritionnel maternel déséquilibré et carencé en AGPI n-3 induit des altérations cognitives et électrophysiologiques chez le nourrisson et dans des modèles murins de carence nutritionnelle. Nous nous intéressons à l’impact d’une intervention nutritionnelle au cours du développement et comment un régime déséquilibré en AGPI n-3 altère les réseaux neuronaux et la cognition, en étudiant les mécanismes moléculaires et en prenant en compte le sexe. Pour cela différents modèles sont utilisés 1) les souriceaux sont carencés en AGPI pendant le développement puis exposés à une diète riche en AGPI n-3 au sevrage ; 2) développer un modèle de carence locale par injection virale bloquant l’expression de l’élongase ELOVL2 (impliquée dans la synthèse des AGPI à longues chaînes) dans les astrocytes pour évaluer l’impact sur les propriétés des neurones environnants. Nos résultats suggèrent qu’un changement de statut nutritionnel d’une carence vers un régime riche en AGPI n-3 au sevrage restaure 1) la plasticité synaptique à long terme dans l’hippocampe chez les mâles et les femelles, 2) la cognition ainsi que les taux d’acides gras dans le cerveau mais de manière différentielle entre les deux sexes. Dans la seconde partie des résultats, une variation locale de la synthèse des AGPI dans l’astrocyte modifie l’excitabilité des neurones sans modifier les taux d’acides gras dans la structure cérébrale tout en modifiant certains critères de comportement émotionnel.