title: Characterization of human cortical gene expression in relation to glucose utilization.
abstract: OBJECTIVE
  Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expression and to examine the evolutionary history of genes differentially expressed as a function of age.
  
  
  METHODS
  We used microarrays to determine age-related patterns of mRNA expression in human cerebral cortical samples ranging from infancy to adulthood. In contrast to previous developmental gene expression studies of human neocortex that relied on postmortem tissue, we measured mRNA expression from the nondiseased margins of surgically resected tissue. We used regression models designed to identify transcripts that followed significant linear or curvilinear functions of age and used population genetics techniques to examine the evolution of these genes.
  
  
  RESULTS
  We identified 40 transcripts with significant age-related trajectories in expression. Ten genes have documented roles in nervous system development and energy metabolism, others are novel candidates in brain development. Sixteen transcripts showed similar patterns of expression, characterized by decreasing expression during childhood. Comparative genomic analyses revealed that the regulatory regions of three genes have evidence of adaptive evolution in recent human evolution.
  
  
  CONCLUSIONS
  These findings provide evidence that a subset of genes expressed in the human cerebral cortex broadly mirror developmental patterns of cortical glucose consumption. Whether there is a causal relationship between gene expression and glucose utilization remains to be determined.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Kirstin N
authors.initials: KN
authors.lastname: Sterner
authors.forename: Michael R
authors.initials: MR
authors.lastname: McGowen
authors.forename: Harry T
authors.initials: HT
authors.lastname: Chugani
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Chet C
authors.initials: CC
authors.lastname: Sherwood
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kuzawa
authors.forename: Amy M
authors.initials: AM
authors.lastname: Boddy
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Raaum
authors.forename: Amy
authors.initials: A
authors.lastname: Weckle
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.forename: Morris
authors.initials: M
authors.lastname: Goodman
authors.forename: Derek E
authors.initials: DE
authors.lastname: Wildman
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006803:Human Development / Q000502:physiology*; D006801:Humans; D007223:Infant; D008251:Macaca; D008297:Male; D046228:Microarray Analysis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005947:Glucose