Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups
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 it...
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00046/full |
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| author | Yohan van de Looij Yohan van de Looij Camille Larpin Jan-Harry Cabungcal Eduardo F. Sanches Audrey Toulotte Kim Q. Do Stéphane V. Sizonenko |
| author_facet | Yohan van de Looij Yohan van de Looij Camille Larpin Jan-Harry Cabungcal Eduardo F. Sanches Audrey Toulotte Kim Q. Do Stéphane V. Sizonenko |
| author_sort | Yohan van de Looij |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T19:03:53Z |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-23T19:03:53Z |
| publishDate | 2019-02-01 |
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| spelling | doaj.art-827954e2f52141c68ef9f467b3d5761d2022-12-21T17:34:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-02-011010.3389/fendo.2019.00046436724Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat PupsYohan van de Looij0Yohan van de Looij1Camille Larpin2Jan-Harry Cabungcal3Eduardo F. Sanches4Audrey Toulotte5Kim Q. Do6Stéphane V. Sizonenko7Division of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, SwitzerlandLaboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandDivision of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, Lausanne, SwitzerlandDivision of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, SwitzerlandDepartment of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, Lausanne, SwitzerlandDivision of Child Development and Growth, Department of Pediatrics, School of Medicine, University of Geneva, Geneva, SwitzerlandIntroduction: 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.https://www.frontiersin.org/article/10.3389/fendo.2019.00046/fullintrauterine growth restrictioncaloric restrictionlactoferrinneuroprotectionmagnetic resonance imaging |
| spellingShingle | Yohan van de Looij Yohan van de Looij Camille Larpin Jan-Harry Cabungcal Eduardo F. Sanches Audrey Toulotte Kim Q. Do Stéphane V. Sizonenko Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups Frontiers in Endocrinology intrauterine growth restriction caloric restriction lactoferrin neuroprotection magnetic resonance imaging |
| title | Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups |
| title_full | Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups |
| title_fullStr | Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups |
| title_full_unstemmed | Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups |
| title_short | Nutritional Intervention for Developmental Brain Damage: Effects of Lactoferrin Supplementation in Hypocaloric Induced Intrauterine Growth Restriction Rat Pups |
| title_sort | nutritional intervention for developmental brain damage effects of lactoferrin supplementation in hypocaloric induced intrauterine growth restriction rat pups |
| topic | intrauterine growth restriction caloric restriction lactoferrin neuroprotection magnetic resonance imaging |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00046/full |
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