Whose expression decreases with age, which may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival. Epigenetic modifications also occur, as human brain aging is accompanied by a global promoter hypomethylation and hypermethylation of certain promoters, including those for brain derived neurotrophic factor and synaptophysin. Lipids are constituents of brain cell membranes; their metabolism consumes approximately 25% of the brain’s ATP, and contribute to Axitinib 319460-85-0 neurotransmission and gene transcription. Furthermore, neurodevelopmental and neurodegenerative diseases have been associated with disturbances in brain lipid composition and related enzymes. Therefore, we thought it of interest to examine the expression during brain development and aging of a limited number of genes involved in lipid metabolism. We focused on the pathways of two polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, within their respective coupled metabolic cascades. In the brain, AA and DHA are mainly esterified in the stereospecifically numbered -2 position of phospholipids, and in triacylglycerols and cholesteryl esters to a lesser extent. During neurotransmission, AA and DHA may be hydrolyzed from phospholipids by receptor-mediated activation of specific phospholipases A2. For example, Ca2+-dependent cytosolic cPLA2 and Ca2+-independent iPLA2 selectively release AA and DHA, respectively. These PLA2s belong to large families and are found in the brain within neurons and astrocytes. At synapses, cPLA2 co-localizes with cyclooxygenase -2, which converts the AA to eicosanoids including prostaglandin E2. Once released by a selective PLA2, unesterified AA and DHA may be recycled into phospholipid by an acyltransferase following its activation by an acyl-CoA synthetase to acyl-CoA. ACSLs and acyltransferases also belong to enzyme families with varying specificities to AA compared with DHA. ACSL4 is more selective for AA, while ACSL6 is more selective for DHA. The lysophosphatidylcholine acyltransferase LPCAT3 is more selective for AA, LPCAT4 for DHA. Another fraction of unesterified AA and DHA in brain undergoes enzymatic oxidation within distinct metabolic cascades, or non-enzymatic loss to reactive oxygen species and other bioactive products. COXs, lipoxygenases, and cytochrome P450 epoxygenases convert AA to eicosanoids such as prostaglandins or leukotrienes, involved in inflammatory responses, and DHA to neuroprotectins and resolvins, which show neuroprotective properties. In the present study, we focused on transcriptional regulation of PUFA metabolizing enzymes during human development and aging. We used the BrainCloud database, which contains mRNA expression levels of 30,176 gene expression probes. This database was constructed from brains of 269 subjects without a neuropathological or a neuropsychiatric diagnosis, with ages ranging from the fetal period to 78 years. We examined age-related expression of 34 genes largely involved in deacylation-reacylation and enzymatic oxidation of AA and DHA. Based on the literature from AA would increase with aging, while expression of genes involved with neuroprotectin.