Expression of Cannabinoid CB1 receptors in models of diabetic neuropathy

Zhang, Fan; Hong, Shuangsong; Stone, Vicki; Smith, Paula

Abstract

A clearer understanding of the mechanisms underlying the development and progression of diabetic neuropathy is likely to indicate new directions for the treatment of this complication of diabetes. In the present study we investigated the expression of cannabinoid CB1 receptors in models of diabetic neuropathy. PC12 cells were differentiated into a neuronal phenotype with nerve growth factor (NGF, 50 ng/ml) in varying concentrations of glucose (5.5 to 50 mM). CB1 receptor expression was studied at the mRNA level by RT-PCR, and at the protein level via immunohistochemical and Western blot analysis. CB1 expression was also compared in dorsal root ganglia (DRG) removed from streptozotocin (STZ)-induced diabetic rats versus control animals. Total neurite length induced by NGF was reduced in cells cultured in 20 to 50 mM glucose at day 6 (P < 0.01 versus 5.5 mM; n = 6). Cell viability assays conducted in parallel on day 6 confirmed that the total cell numbers were not significantly different among the various glucose concentrations (P = 0.86; n = 12). RT-PCR, immunohistochemical, and Western blot analysis all revealed down-regulation of the CB1 receptor in cells treated with high glucose (P < 0.05; n = 4–5 for each), and in DRG removed from diabetic rats compared with controls (P < 0.01; n = 5 for immunohistochemistry, and n = 3 for Western blot). These results suggest that high glucose concentrations are associated with decreased expression of CB1 receptors in nerve cells. Given the neuroprotective effect of cannabinoids, a decline in CB1 receptor expression may contribute to the neurodegenerative process observed in diabetes.

Citation

Zhang, F., Hong, S., Stone, V., & Smith, P. (2007). Expression of Cannabinoid CB1 receptors in models of diabetic neuropathy. Journal of Pharmacology and Experimental Therapeutics, 323, 508-515. https://doi.org/10.1124/jpet.107.128272

• Journal Article Type: Article
• Publication Date: Nov 1, 2007
• Deposit Date: Jun 27, 2008
• Print ISSN: 0022-3565
• Electronic ISSN: 1521-0103
• Publisher: American Society for Pharmacology and Experimental Therapeutics
• Peer Reviewed: Peer Reviewed
• Volume: 323
• Pages: 508-515
• DOI: https://doi.org/10.1124/jpet.107.128272
• Keywords: Diabetes; Neuropathy; Cannabinoid CB1 receptors; Relationships
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/1669
• Publisher URL: http://jpet.aspetjournals.org/cgi/reprint/jpet.107.128272v1