Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism

Abstract

Background: Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf ) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown. Methods: IUGR was induced through maternal dexamethasone infusion (100 μg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pups growth was monitored, and pup brain metabolism and gene expression were studied using in vivo 1 H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7. results: Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pup (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (γ-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation. conclusion: Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes.

Lactoferrin during lactation protects the immature hypoxic‐ischemic rat brain

“…In addition to Lf's known actions of delaying preterm delivery,13–15 preventing neonatal sepsis and necrotizing enterocolitis,59 we have here demonstrated in a preclinical HI model of preterm brain damage that Lf can also protect the preterm brain against HI injury. This adds to prior studies showing that Lf has the potential to reduce altered brain development induced by intrauterine growth restriction 16. An important feature of this study is that Lf is given to the dams during the lactation period from P0.…”

Lactoferrin from Milk: Nutraceutical and Pharmacological Properties

“…In addition, iron-bLf administration is able to decrease the onset of dexamethasone (DEX) induced IntraUterine Growth Restriction (IUGR) that alters levels of brain metabolites (γ-aminobutyric acid, glutamate, N -acetylaspartate, and N -acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors), leading to defective hippocampal development and later cognitive impairment [130]. …”

Lactoferrin and prematurity: a promising milk protein?

“…Rat and ovine models of glucocorticoid exposure during gestation have been shown to cause IUGR (LaBorde et al 1992) and brain weight, hypomyelination (Dunlop et al 1997), and a delay in the differentiation of brain tissues (Basilious et al 2015; Van den Hove et al 2006b). Using rat IUGR/stress model of dexamethasone (DEX) exposure during late gestation, hippocampal metabolism and gene expression was investigated (Somm et al 2014). Attention of the study was on hippocampus at P7 (a significant time point corresponding to a late neuronal proliferative phase) since this brain limbic region involved in the long term memory process contains high levels of glucocorticoid receptors, making it particularly vulnerable to DEX-induced foetal programming (Noorlander et al 2008; Uno et al 1994).…”

“…Attention of the study was on hippocampus at P7 (a significant time point corresponding to a late neuronal proliferative phase) since this brain limbic region involved in the long term memory process contains high levels of glucocorticoid receptors, making it particularly vulnerable to DEX-induced foetal programming (Noorlander et al 2008; Uno et al 1994). Nutritional supplementation with Lf to the dam during gestation and lactation reversed the effects of maternal exposure to dexamethasone (Somm et al 2014). At P7, both levels of glutamate and NAA ( 1 H-MRS), microstructure with neuronal density recovery in the hippocampus and gene expression of BDNF and MT1 were altered in DEX animals, but normalized by Lf supplementation during gestation and lactation.…”