title: Low birth weight associates with hippocampal gene expression.
abstract: Birth weight predicts the lifetime risk for psychopathology suggesting that the quality of fetal development influences the predisposition for mental disorders. The connectivity and synaptic network of the hippocampus are implicated in depression, schizophrenia and anxiety. We thus examined the underlying molecular adaptations in the hippocampus as a function of the fetal conditions associated with low birth weight. We used tissues from the non-human primate, Macaca fascicularis, to identify changes in hippocampal gene expression early in postnatal development associated with naturally occurring low compared with normal birth weight. Microarrays were used to analyze gene expression and DNA methylation in the hippocampus of five low- and five normal-birth weight neonates. Real-time PCR was employed to validate differentially expressed genes. Birth weight associated with altered global transcription in the hippocampus. Hierarchical clustering of gene expression profiles from 24,154 probe sets grouped all samples except one by their birth weight status. Differentially expressed genes were enriched in biological processes associated with neuronal projection, positive regulation of transcription and apoptosis. About 4% of the genes with differential expression co-varied with DNA methylation levels. The data suggest that low birth weight is closely associated with hippocampal gene expression with a small epigenetic underpinning by DNA methylation in neonates. The data also provide a potential molecular basis for the developmental origin of an enhanced risk for mental disorders.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore. Electronic address: janpaul@sics.a-star.edu.sg.
authors.forename: J P
authors.initials: JP
authors.lastname: Buschdorf
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: M L
authors.initials: ML
authors.lastname: Ong
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: S X
authors.initials: SX
authors.lastname: Ong
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: MacIsaac
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: K
authors.initials: K
authors.lastname: Chng
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada; Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Kobor
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore; Canadian Neuroepigenetics Network, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec H4H 1R3, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Meaney
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: J D
authors.initials: JD
authors.lastname: Holbrook
mesh_terms: D000818:Animals; D005260:Female; D011247:Pregnancy; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D008252:Macaca fascicularis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012306:Risk; D000831:Animals, Newborn
keywords: DNA methylation; hippocampus; low birth weight; mental disorders; microarray