期刊论文详细信息
BMC Neuroscience
Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex
Cynthia Shannon Weickert2  Maree Webster3  Jonna Lind1  Leonora E Long2 
[1] Karolinska Institutet, Stockholm, Sweden;University of New South Wales, Sydney, NSW, 2031, Australia;Stanley Medical Research Institute, Rockville, MD, 20815, USA
关键词: Inhibitory interneuron;    Endocannabinoid;    Development;    CB1 receptor;   
Others  :  1170615
DOI  :  10.1186/1471-2202-13-87
 received in 2012-02-04, accepted in 2012-06-28,  发布年份 2012
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【 摘 要 】

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.

【 授权许可】

   
2012 Long et al.; licensee BioMed Central Ltd.

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