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Open Access Highly Accessed Research article

Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex

Leonora E Long123, Jonna Lind4, Maree Webster5 and Cynthia Shannon Weickert123*

Author Affiliations

1 Schizophrenia Research Institute, Darlinghurst, NSW, 2010, Australia

2 Neuroscience Research Australia, Barker St, Randwick, NSW, 2031, Australia

3 University of New South Wales, Sydney, NSW, 2031, Australia

4 Karolinska Institutet, Stockholm, Sweden

5 Stanley Medical Research Institute, Rockville, MD, 20815, USA

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BMC Neuroscience 2012, 13:87  doi:10.1186/1471-2202-13-87

Published: 24 July 2012

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 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).

Results

CB1R 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 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.

Keywords:
CB1 receptor; Development; Endocannabinoid; Inhibitory interneuron