Maternal n-3 Polyunsaturated Fatty Acid Enriched Diet Commands Fatty Acid Composition in Postnatal Brain and Protects from Neonatal Arterial Focal Stroke

Tetyana Chumak,Ulrika Sjöbom,Joakim Ek,Matthieu J Lecuyer,Anders K Nilsson,Pernilla Svedin,Carina Mallard,Andre Obenaus,Maryam Ardalan,Joel Faustino,Zinaida S Vexler

doi:10.1007/s12975-021-00947-9

Abstract

The fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA). In adult animals, n-3 PUFA ameliorates stroke-mediated brain injury, but the modulatory effects of different PUFA content in maternal diet on focal arterial stroke in neonates are unknown. This study explored effects of maternal n-3 or n-6 enriched PUFA diets on neonatal stroke outcomes. Pregnant mice were assigned three isocaloric diets until offspring reached postnatal day (P) 10–13: standard, long-chain n-3 PUFA (n-3) or n-6 PUFA (n-6) enriched. Fatty acid profiles in plasma and brain of mothers and pups were determined by gas chromatography–mass spectrometry and cytokines/chemokines by multiplex protein analysis. Transient middle cerebral artery occlusion (tMCAO) was induced in P9-10 pups and cytokine and chemokine accumulation, caspase-3 and calpain-dependent spectrin cleavage and brain infarct volume were analyzed. The n-3 diet uniquely altered brain lipid profile in naïve pups. In contrast, cytokine and chemokine levels did not differ between n-3 and n-6 diet in naïve pups. tMCAO triggered accumulation of inflammatory cytokines and caspase-3-dependent and -independent cell death in ischemic-reperfused regions in pups regardless of diet, but magnitude of neuroinflammation and caspase-3 activation were attenuated in pups on n-3 diet, leading to protection against neonatal stroke. In conclusion, maternal/postnatal n-3 enriched diet markedly rearranges neonatal brain lipid composition and modulates the response to ischemia. While standard diet is sufficient to maintain low levels of inflammatory cytokines and chemokines under physiological conditions, n-3 PUFA enriched diet, but not standard diet, attenuates increases of inflammatory cytokines and chemokines in ischemic-reperfused regions and protects from neonatal stroke.Graphic

Highlights

The developing fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA), and neonatal plasma PUFA levels correlate with maternal plasma and breast milk concentrations [1, 2]
We show that maternal n-3 PUFA enriched diet under physiological conditions dictates unique brain lipid composition without major effects on cytokine and chemokine levels, but it attenuates neuroinflammation induced by transient middle cerebral artery occlusion and provides a neuroprotective milieu for neonatal stroke
Non-hierarchic grouping using dimension reducing principal component analysis (PCA), in turn, showed that maternal diet markedly affected clustering of fatty acids in a n-3–specific manner in neonatal brain tissue compared to pups from mothers on standard and n-6 diets (Fig. 1a)

Summary

Introduction

Materials and MethodsThe developing fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA), and neonatal plasma PUFA levels correlate with maternal plasma and breast milk concentrations [1, 2]. We show that maternal n-3 PUFA enriched diet under physiological conditions dictates unique brain lipid composition without major effects on cytokine and chemokine levels, but it attenuates neuroinflammation induced by transient middle cerebral artery occlusion (tMCAO) and provides a neuroprotective milieu for neonatal stroke.

Results

Conclusion