Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups

Article Article scientifique Article Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups eng 2019 author Van De Looij Yohan 652102 author Larpin Camille Marie 834626 author Cabungcal Jan-Harry author Farias Sanches Eduardo 842583 author Aebi Toulotte Audrey 22162 author Do Kim Q author Sizonenko Stéphane 0000-0003-0093-8747 24332 46 10.3389/fendo.2019.00046 30800096 1664-2392 Introduction: Intrauterine Growth Restriction (IUGR) refers to an impaired development of the fetus and hence results in adverse neurodevelopmental and psychiatric consequences later in life. Lactoferrin (Lf) is a glycoprotein present in milk that has already shown neuroprotective effects through its anti-inflammatory and antioxidant properties on impaired developing brains. The aim of this study was to characterize a rat model of IUGR and assess the neuroprotective effect of a nutritional supplementation with bovine Lf during pregnancy and lactation on this model. Methods: A model of 50% gestational caloric restriction (CR) was used. Three groups were designed, and pregnant rats had either ad libitum access to food (control group, CTL) or 50% of the controls' intake (restricted group, IUGR). The diet was isocaloric and supplemented with bovine Lf for the caloric restricted dams (restricted-Lf, IUGR_Lf). At postnatal day 7 and 21, advanced ex-vivo diffusion MRI techniques at 9.4T were used to investigate brain cortical and white matter microstructure. Further, genes and proteins involved in structure (synaptophysin, MBP), microglia (Iba-1), metabolism (MCT2, βCaMKII) and apoptosis (Bcl-2) were analyzed in the cortex and striatum. In the cortex, the number of parvalbumin immunoreactive interneurons and their perineuronal nets were quantified. Behavioral tests were performed at P31. Results: Effects of the CR were significant in the cortex and striatum with reduction of synaptophysin (marker of synaptogenesis) at P7 and MBP (marker of myelin) at P21 in the cortex. Indeed, MCT2 (energy metabolism), Bcl-2 (anti-apoptotic protein) and βCaMKII (synapse activity) expressions were reduced in IUGR groups at P7. In the striatum NG2 (marker of oligodendrocyte precursor cells) and Bcl-2 at P7 as well as βCaMKII at P21 were decreased following IUGR and restored by Lf. Cortical microstructure was impaired following CR with partial effect of Lf. Lf prevented oxidative stress induced parvalbumin interneurons impairments whereas striatum and external capsule showed alterations in microstructure depicted by diffusion MRI, which were also partially reversed by Lf. Discussion and Conclusion: The model of 50% caloric restriction induced mild impairment partially reversed by nutritional intervention using Lf during pregnancy and lactation. Intrauterine growth restriction Caloric restriction Lactoferrin Neuroprotection Magnetic resonance Imaging Dewey 618 Swiss National Science Foundation 33CM30-124101/140334 CH 58 Département de pédiatrie, gynécologie et obstétrique 223 false 150 L'imagerie cérébrale 184 https://figshare.com/collections/Nutritional_Intervention_for_Developmental_Brain_Damage_Effects_of_Lactoferrin_Supplementation_in_Hypocaloric_Induced_Intrauterine_Growth_Restriction_Rat_Pups/4393985 Frontiers in Endocrinology 10 0ab78c29-bfd6-4aa4-821c-aab85740d99e Article (Published version) Public fendo-10-00046.pdf 2876223 application/pdf CC BY openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups	Frontiers in Endocrinology			2019	355	180

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Larpin, Camille Marie