title: Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.
abstract: BACKGROUND
  The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.
  
  
  OBJECTIVE
  AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.
  
  
  METHODS
  The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.
  
  
  RESULTS
  Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.
  
  
  CONCLUSIONS
  Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Veronica H
authors: VH
authors: Ryan
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Christopher T
authors: CT
authors: Primiani
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Jagadeesh S
authors: JS
authors: Rao
authors: Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Kwangmi
authors: K
authors: Ahn
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Stanley I
authors: SI
authors: Rapoport
authors: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Helene
authors: H
authors: Blanchard
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D016718:Arachidonic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid