Abstract
Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.
Highlights
We found that human ependymal region consistently expresses CB1 cannabinoid receptor (CNR1 gene; Table 1)
CB1 receptor could be the target of locally produced 2-AG, since we found expression of enzymes related with 2-AG synthesis and degradation: diacylglycerol lipase α (DAGLA), diacylglycerol lipase β (DAGLB), monoacylglycerol lipase (MGLL) and abhydrolase domain-containing proteins – 6 (ABHD6) and –12 (ABHD12)
We could not find consistent expression of enzymes related with direct anandamide synthesis or degradation (NAPE-phospholipase D and fatty acid amide hydrolase, respectively)
Summary
We found that human ependymal region consistently expresses CB1 cannabinoid receptor (CNR1 gene; Table 1). We observed expression (but not enrichment) of PPAR-α , another cannabinoid-related receptor[1], in human ependymal region[9]. We obtained some sections from adult individuals in which parts of the central canal were patent In those sections, we found ependymal cells with high expression of CB1 receptors lining the canal (Fig. 1L–N), resembling those CB1HIGH cells described for rats and mice[6]. We found ependymal cells with high expression of CB1 receptors lining the canal (Fig. 1L–N), resembling those CB1HIGH cells described for rats and mice[6] These cells were mostly GFAP-, except for a very dim expression at the apical pole (Fig. 1N), in contrast with strongly GFAP+ cells embeded in the ependymal layer (Fig. 1M). In the majority of adult ependyma, CB1 is enriched in astrocyte domains, and cannabinoids may play a different role, that still might be relevant, in terms of homeostasis maintenance and response to injury
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