Zhang, Fan, Hong, Shuangsong, Stone, Vicki and Smith, Paula (2007) Expression of Cannabinoid CB1 receptors in models of diabetic neuropathy. Journal of Pharmacology and Experimental Therapeutics, 323 (2). pp. 508-515. ISSN 15210103

Abstract/Description

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 20–50 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 between the various glucose concentrations (P=0.86; n=12).
RT-PCR, immunohistochemical and Western blot analysis all revealed downregulation of the CB1 receptor in cells treated with high glucose (P<0.05; n=5 for each), and in DRG removed from diabetic rats compared to controls (P<0.01; n=3 for immunohistochemistry, and n=5 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.

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