Abstract
BackgroundThe 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.HypothesisAA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.MethodsThe 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.ResultsExpression 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.ConclusionsCoordinated 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.
Highlights
The human brain undergoes marked structural and functional changes after birth, such as synaptic growth followed by synaptic pruning, progressive myelination, neuroplasticity, and changes in energy metabolism, which likely underlie maturation and maintenance of cognitive and behavioral abilities [1,2,3,4]
In a genome-wide aging study of brain gene expression in humans and rhesus macaques, Somel et al found that expression variations of energy metabolism, synaptic plasticity, vesicular transport, and mitochondrial functions in the prefrontal cortex translated to related biological functions of the gene products [12]
We focused on the pathways of two polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:6n-6) and docosahexaenoic acid (DHA, 22:6n-3), within their respective coupled metabolic cascades
Summary
The human brain undergoes marked structural and functional changes after birth, such as synaptic growth followed by synaptic pruning, progressive myelination, neuroplasticity, and changes in energy metabolism, which likely underlie maturation and maintenance of cognitive and behavioral abilities [1,2,3,4]. In a genome-wide aging study of brain gene expression in humans and rhesus macaques, Somel et al found that expression variations of energy metabolism, synaptic plasticity, vesicular transport, and mitochondrial functions in the prefrontal cortex translated to related biological functions of the gene products [12]. Hypothesis: AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging
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