Cited by 46Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsPeripheral Neuropathies and Disorders

Expression of cannabinoid CB1 receptors in models of diabetic neuropathy

Zhang, Fan, Hong, Shuangsong, Stone, Vicki, Smith, Paula J.W.·2007·The Journal of Pharmacology and Experimental Therapeutics

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 CB(1) 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 (5.5-50 mM). CB(1) receptor expression was studied at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level via immunohistochemical and Western blot analysis. CB(1) expression was also compared in dorsal root ganglia (DRG) removed from streptozotocin-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 CB(1) 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 CB(1) receptors in nerve cells. Given the neuroprotective effect of cannabinoids, a decline in CB(1) receptor expression may contribute to the neurodegenerative process observed in diabetes.

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Crossref · 10.1124/jpet.107.128272

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Authors
Zhang, F., Hong, S., Stone, V., & Smith, P. J. W.
Affiliations
Edinburgh Napier University (GB)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2007-11
Volume
323
Issue
2
Pages
508-515
ISSN
0022-3565 (ISSN-L)
OpenAlex
W2113184132
Cited by
46
References
40
Citations by year
2022: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 9
FWCI
2.44
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
CB1 receptor, diabetic neuropathy, high glucose, nerve growth factor, PC12 cells, dorsal root ganglia, streptozotocin-induced diabetes, neurite outgrowth, receptor down-regulation, neuroprotection, neurodegeneration
MeSH terms
Animals, Diabetic Neuropathies, Male, RNA, Messenger, Neurites, PC12 Cells, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, TRPV Cation Channels, Rats

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