title: Limited effects of preterm birth and the first enteral nutrition on cerebellum morphology and gene expression in piglets.
abstract: Preterm pigs show many signs of immaturity that are characteristic of preterm infants. In preterm infants, the cerebellum grows particularly rapid and hypoplasia and cellular lesions are associated with motor dysfunction and cognitive deficits. We hypothesized that functional brain delays observed in preterm pigs would be paralleled by both structural and molecular differences in the cerebellum relative to term born piglets. Cerebella were collected from term (n = 56) and preterm (90% gestation, n = 112) pigs at 0, 5, and 26 days after birth for stereological volume estimations, large-scale qPCR gene expression analyses (selected neurodevelopmental genes) and western blot protein expression analysis (Sonic Hedgehog pathway). Memory and learning was tested using a T-maze, documenting that preterm pigs showed delayed learning. Preterm pigs also showed reduced volume of both white and gray matter at all three ages but the proportion of white matter increased postnatally, relative to term pigs. Early initiation of enteral nutrition had limited structural or molecular effects. The Sonic Hedgehog pathway was unaffected by preterm birth. Few differences in expression of the selected genes were found, except consistently higher mRNA levels of Midkine, p75, and Neurotrophic factor 3 in the preterm cerebellum postnatally, probably reflecting an adaptive response to preterm birth. Pig cerebellar development appears more affected by postconceptional age than by environmental factors at birth or postnatally. Compensatory mechanisms following preterm birth may include faster white matter growth and increased expression of selected genes for neurotrophic factors and regulation of angiogenesis. While the pig cerebellum is immature in 90% gestation preterm pigs, it appears relatively mature and resilient toward environmental factors.
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Bergström
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospitals, Copenhagen, Denmark.
authors.forename: Sanne S
authors.initials: SS
authors.lastname: Kaalund
authors.affiliation: Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Skovgaard
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Andersen
authors.affiliation: Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg Hospitals, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Ann
authors.initials: A
authors.lastname: Rosenørn
authors.affiliation: Danone Nutricia Early Life Nutrition, Nutricia Research, Utrecht, the Netherlands Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Ruurd M
authors.initials: RM
authors.lastname: van Elburg
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gorm O
authors.initials: GO
authors.lastname: Greisen
authors.affiliation: Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark pts@sund.ku.dk.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D001522:Behavior, Animal; D001699:Biometry / Q000379:methods; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D004750:Enteral Nutrition / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005865:Gestational Age; D053823:Hedgehog Proteins / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D010288:Parenteral Nutrition / Q000379:methods; D034421:Sus scrofa
chemical_list: D053823:Hedgehog Proteins
keywords: Enteral and parenteral nutrition; neonatal brain development; postconceptional age; prematurity