title: Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex.
abstract: BACKGROUND
  Endocannabinoids provide control over cortical neurotransmission. We investigated the developmental expression of key genes in the endocannabinoid system across human postnatal life and determined whether they correspond to the development of markers for inhibitory interneurons, which shape cortical development. We used microarray with qPCR validation and in situ hybridisation to quantify mRNA for the central endocannabinoid receptor CB(1)R, endocannabinoid synthetic enzymes (DAGLα for 2-arachidonylglycerol [2-AG] and NAPE-PLD for anandamide), and inactivating enzymes (MGL and ABHD6 for 2-AG and FAAH for anandamide) in human dorsolateral prefrontal cortex (39 days - 49 years).
  
  
  RESULTS
  CB(1)R mRNA decreases until adulthood, particularly in layer II, after peaking between neonates and toddlers. DAGLα mRNA expression is lowest in early life and adulthood, peaking between school age and young adulthood. MGL expression declines after peaking in infancy, while ABHD6 increases from neonatal age. NAPE-PLD and FAAH expression increase steadily after infancy, peaking in adulthood.
  
  
  CONCLUSIONS
  Stronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB(1)R mRNA may occur within the first few years of human life. After adolescence, higher mRNA levels of the anandamide synthetic and inactivating enzymes NAPE-PLD and FAAH suggest that a late developmental switch may occur where anandamide is more strongly regulated after adolescence than earlier in life. Thus, expression of key genes in the endocannabinoid system changes with maturation of cortical function.
authors: Schizophrenia Research Institute, Darlinghurst, NSW 2010, Australia.
authors: Leonora E
authors: LE
authors: Long
authors: Jonna
authors: J
authors: Lind
authors: Maree
authors: M
authors: Webster
authors: Cynthia Shannon
authors: CS
authors: Weickert
mesh_terms: D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D063388:Endocannabinoids / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007223:Infant; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D010739:Phospholipase D; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C540878:ABHD6 protein, human; C480280:DAGLA protein, human; C527163:Napepld protein, rat