Maternal α-linolenic acid availability during gestation and lactation alters the postnatal hippocampal development in the mouse offspring

The availability of n3 polyunsaturated fatty acids is essential for perinatal brain development. While the roles of docosahexaenoic acid (the most abundant n3 species) were extensively described, less is known about the role of alpha-linolenic acid (ALA), which is the initial molecular species undergoing elongation and desaturation within the n3 pathways. This study describes the association between maternal ALA availability during gestation and lactation, and alterations in hippocampal development (dentate gyrus) in the mouse male offspring, at the end of lactation (postnatal day 19, P19). Postnatal ALA supplementation increased cell proliferation (36% more proliferating cells compared to a control group) and early neuronal differentiation, while postnatal ALA deficiency increased cellular apoptosis within the dentate gyrus of suckling pups (61% more apoptotic cells compared to a control group). However, maternal ALA deficiency during gestation prevented the increased neurogenesis induced by postnatal supplementation. Fatty acid analysis revealed that ALA supplementation increased the concentration of the n3 species in the maternal liver and serum, but not in the brain of the offspring, excepting for ALA itself. nterestingly, ALA supplementation also increased the concentration of dihomo gamma-linolenic acid (an n6 species) in the P19 brains, but not in maternal livers or serum. In conclusion, postnatal ALA supplementation enhances neurogenesis in the dentate gyrus of the offspring at postnatal day 19, but its beneficial effects are offset by maternal ALA deficiency during gestation. These results suggest that ALA is required in both fetal and postnatal stages of brain development. (Authors abstract)
Omega-3 fatty acids (FA) play an essential role in brain development and cognition during fetal development and after birth and little is known of ALA in this area. A limited number of in vitro and in vivo studies indicate that ALA may act as a signaling molecule, activating a variety of pathways, including IGF signal transduction and mitogen-activated protein kinase pathways. Very little is known about the relationship between postnatal brain development and ALA maternal intakes during gestation and lactation. In the present study the hypothesis that the maternal supplementation with flaxseed oil (containing more than 50% ALA) during lactation, alters hippocampal neurogenesis in the offspring at the end of lactation period (postnatal day 19, P19). In addition, whether maternal flaxseed oil availability, prior and during gestation, modulates this outcome was studied. The maternal ALA supplementation from flaxseed oil increased cell proliferation and early neuronal differentiation within the DG of suckling pups. The results indicated that ALA supplementation exerts an active influence upon neurogenesis in both fetal and lactating periods of DG development. In contrast with the changes in neurogenesis, apoptosis (as determined by activated caspase-3 labeling) was increased only in the D�D group of pups (a 61% increase when compared to the C�C group receiving a standard diet). However, this increase was offset by the maternal postnatal ALA supplementation. Therefore, apoptosis in DG, as measured at postnatal day 19 (P19), seems to exclusively depend upon the ALA intake during lactation. This outcome suggests that ALA availability during gestation has a negligible influence, if any, upon postnatal apoptosis within the DG in offspring at P19. Within the maternal liver ALA, EPA, and DPA were increased in both supplemented groups during lactation, regardless the ALA availability during gestation. This indicates that the content of these fatty acids reflects the actual dietary maternal intakes (at day 19 of lactation) rather than any historical intakes during gestation. In the present study the outcomes induced by maternal flaxseed oil supplementation to the development of the DG in the suckling pups did not necessarily correlate with the actual fatty acid levels in the P19 brains. Results indicated that ALA is required continuously during both fetal and postnatal stages of brain development, and that supplementation only during lactation may not be sufficient for its established outcomes if the maternal organism is depleted during gestation. Further studies are required to determine the optimal requirements and timing regarding the administration ALA both gestation and lactation, and the degree of relevance when using animal models for defining human requirements. (Editors comments)