title: Impact of dietary n-3 polyunsaturated fatty acids on cognition, motor skills and hippocampal neurogenesis in developing C57BL/6J mice.
abstract: Maternal intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) is critical during perinatal development of the brain. Docosahexaenoic acid (DHA) is the most abundant n-3 PUFA in the brain and influences neuronal membrane function and neuroprotection. The present study aims to assess the effect of dietary n-3 PUFA availability during the gestational and postnatal period on cognition, brain metabolism and neurohistology in C57BL/6J mice. Female wild-type C57BL/6J mice at day 0 of gestation were randomly assigned to either an n-3 PUFA deficient diet (0.05% of total fatty acids) or an n-3 PUFA adequate diet (3.83% of total fatty acids) containing preformed DHA and its precursor α-linolenic acid. Male offspring remained on diet and performed cognitive tests during puberty and adulthood. In adulthood, animals underwent (31)P magnetic resonance spectroscopy to assess brain energy metabolites. Thereafter, biochemical and immunohistochemical analyses were performed assessing inflammation, neurogenesis and synaptic plasticity. Compared to the n-3 PUFA deficient group, pubertal n-3 PUFA adequate fed mice demonstrated increased motor coordination. Adult n-3 PUFA adequate fed mice exhibited increased exploratory behavior, sensorimotor integration and spatial memory, while neurogenesis in the hippocampus was decreased. Selected brain regions of n-3 PUFA adequate fed mice contained significantly lower levels of arachidonic acid and higher levels of DHA and dihomo-γ-linolenic acid. Our data suggest that dietary n-3 PUFA can modify neural maturation and enhance brain functioning in healthy C57BL/6J mice. This indicates that availability of n-3 PUFA in infant diet during early development may have a significant impact on brain development.
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Carola I F
authors.initials: CI
authors.lastname: Janssen
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Martina P C
authors.initials: MP
authors.lastname: Mutsaers
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Bas S W
authors.initials: BS
authors.lastname: de Jong
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands; Department of Geriatrics, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Wiesmann
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Ilse A C
authors.initials: IA
authors.lastname: Arnoldussen
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Geenen
authors.affiliation: Department of Radiology, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical centerr, Nijmegen, The Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Frits A J
authors.initials: FA
authors.lastname: Muskiet
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Nijmegen/Evansville, The Netherlands/IN, USA.
authors.forename: Zeina E
authors.initials: ZE
authors.lastname: Jouni
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Nijmegen/Evansville, The Netherlands/IN, USA.
authors.forename: Eric A F
authors.initials: EA
authors.lastname: van Tol
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Nijmegen/Evansville, The Netherlands/IN, USA.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gross
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, Nijmegen/Evansville, The Netherlands/IN, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berg
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Amanda.Kiliaan@radboudumc.nl.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D000076122:Disks Large Homolog 4 Protein; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000494:pharmacology
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D015525:Fatty Acids, Omega-3; D008565:Membrane Proteins; D016708:Synaptophysin; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D051528:Guanylate Kinases; D015126:8,11,14-Eicosatrienoic Acid
keywords: Animal models; Brain development; Cognition; Neurohistology; Omega-3 fatty acid supplementation; Phosphorus magnetic resonance imaging