Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex

BMC Neuroscience

Research Article

Jonna Lind¹  Leonora E Long²  Cynthia Shannon Weickert²  Maree Webster³ 

[1] Karolinska Institutet, Stockholm, Sweden;Schizophrenia Research Institute, 2010, Darlinghurst, NSW, Australia;Neuroscience Research Australia, Barker St, 2031, Randwick, NSW, Australia;University of New South Wales, 2031, Sydney, NSW, Australia;Stanley Medical Research Institute, 20815, Rockville, MD, USA;

关键词: CB receptor;    Development;    Endocannabinoid;    Inhibitory interneuron;   

DOI  :  10.1186/1471-2202-13-87

 received in 2012-02-04, accepted in 2012-06-28,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEndocannabinoids 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 CB1R, 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).ResultsCB1R 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.ConclusionsStronger endocannabinoid regulation of presynaptic neurotransmission in both supragranular and infragranular cortical layers as indexed through higher CB1R 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.

【 授权许可】

Unknown   
© Long et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.